tert-butyl 3,5,5-trimethylperoxyhexanoate

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

adult fish: sub(lethal) effects

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2017

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:

Please refer to attached QMRF and QPRF Documents.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR R.6

Principles of method if other than guideline:

Calculation of Long-Term toxicity in fish. Software used: ECOSAR 1.11 (EPISUITE) for chemical class "Peroxyester" and "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC(C)(C)OOC(=O)CC(C)CC(C)(C)C

Analytical monitoring:

not required

Test organisms (species):

other: fish

Water media type:

freshwater

Total exposure duration:

30 d

Remarks on exposure duration:

chronic exposure

Key result

Duration:

30 d

Effect conc.:

0.117 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Peroxyester".

Key result

Duration:

30 d

Effect conc.:

0.168 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Neutral Organic SAR (Baseline Toxicity)".

 

ECOSAR v1.11 Class-specific Estimations
ECOSAR Class	Organism	Duration	End Pt	Predicted mg/L (ppm)
Peroxy Esters	Fish	96-hr	LC50	1.181
Peroxy Esters	Daphnid	48-hr	LC50	1.669
Peroxy Esters	Green Algae	96-hr	EC50	0.134
Peroxy Esters	Fish		ChV	0.117 !
Peroxy Esters	Daphnid		ChV	0.236
Peroxy Esters	Green Algae		ChV	0.039

! = exclamation designates: The toxicity value was estimated through application of acute-to-chronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

Validity criteria fulfilled:

yes

Conclusions:

Using ECOSAR v1.11 the long-term toxicity ChV value for fish was calculated to be 0.117 mg/L. The substance is within the applicability domain of the model.

Executive summary:

The long-term toxicity in fish was calculated using ECOSARv 1.11 as part of EPISuite v4.11 from US Environmental Protection Agency.

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descriped using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Reference 2

Endpoint:

fish early-life stage toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The performance of a test for long-term toxicity to fish was considered not scientifically justified. REACH Regulation No. 1907/2006, Annex IX, Sect. 9.1., Col. 1 requests the performance of a Long-term toxicity testing on fish, but based on the following reasons, the long-term toxicity testing of fish was considered scientifically not justified based onREACH, Annex XI, Section 1.2 and 1.3:

Exposure and stability considerations:
TBPIN is not stable in the aquatic environment. Due to the unstable nature of organic peroxides, it can be assumed that upon contact with water and organic matter, the test item undergoes rapid degradation resulting in the formation of respective alcohols and acids. Hydrolysis half-life of TBPIN was determined to be 213.2 hrs (ca. 9 days) at 12 °C, reflecting the worst case half-life determined with TBPIN in this study. Therefore, an abiotic degradation of the test item in the environment is expected.
In addition, the test item was found to be readily biodegradable.

Weight of evidence and QSAR:
Based on available data on toxicity to aquatic organisms, algae was considered to be the most sensitive species with the test item.
A long-term toxicity study on Daphnia magna reveiled a 21-d NOEC of 0.22 mg/L, an EC10 of 0.33 mg/L and an EC50 of 0.58 mg/L. These results are a bit higher then the effect levels obtained in the algae inhibition study, wehre a NOEC of 0.125 mg/L was derived after 72 hours of exposure and an EC50 based on growth rate was determined to be 0.51 mg/L. In the short-term test with Daphnia magna no effects were observed up to the limit dose of 100 mg/L (nominal) or 0.518 mg/L (measured concentration). The results obtained in the short-term test on fish show to be quite higher than the results obtained for the other two species - a 96-h LC50 of 7.03 mg/L and a NOEC of 3 mg/L. Therefore, and for animal welfare reasons, long-term toxicity testing with fish is considered to not improve the database and accordingly the chemical safety assessment. This assumption is further supported by QSAR calculations. Chronic toxicity effect concentrations were estimated with ECOSAR v1.11 for algae, daphnia and fish (For more details please refer to IUCLID Section 6.1.2). The test item was within the applicability domain of the model thus reliability of the results is not affected. ChV values were estimated to be 0.117, 0.236 and 0.039 mg/L for fish, daphnia, and algae, respectively, for the chemical group "Peroxyesters", being in well accordance with experimental data for long-term toxicity in algae and daphnia. Based on calculated values, again algae was predicted with QSAR to be the most sensitive species.

Based on the points outline above, long-term toxicity testing is considered scientifically not justified since the test item is not stable in the aquatic environment, the available data shows that the most sensitive species for the aquatic environment has been already determined and the endpoint is adequately covered with a reliable QSAR estimation..

Furthermore, the Environmental Risk Assessment revealed safe use of the substance throughout its whole life cycle due to very low exposure of the water compartment which is especially based on the following facts:
Organic peroxides, when released into the sewage of a plant production or a downstream user’s plant, are treated with other substances in dedicated sewage treatment plants. The activated sludge stemmed from these sewage treatment plants are then extracted and treated as chemical waste. From the production plant, the release of organic peroxide into the sewage is very limited, not to say completely negligible. The waste water from production plant can be treated on site (at least a physical/chemical treatment, which will neutralize potential residual organic peroxide), which is usually followed by a biological treatment. Regarding the rest of the life cycle, organic peroxides are mainly used as cross-linking agent/polymerization initiator for the production of resins/rubbers/polymers. Based upon the fact that organic peroxides are totally consumed during the process (>99%, which is confirmed by the release factor to sewage for curing agents from OECD ESD n°3), the surface water is not exposed to organic peroxides via the waste water system. As a consequence, the surface water and with this aquatic organisms are not considered to be significantly exposed by the test item.
Additionally, TBPIN is used only as an intermediate at industrial setting for the production of other products and reacts completely through the polymerisation process.

In summary, long-term toxicity testing in a vertebrate species is considered not scientifically justified according to REACH Regulation No. 1907/2006, Annex XI, Sect. 1.1. and 1.3, additionally, no further testing based on the chemical safety assessment according to REACH Annex IX, Sect. 9.1., Col. 2 is considered necessary and is not in line with animal welfare.

Description of key information

Using ECOSAR v1.11 the long-term toxicity ChV value for fish was calculated to be 0.117 mg/L. The substance is within the applicability domain of the model.

Additional information

The performance of a test for long-term toxicity to fish was considered not scientifically justified. REACH Regulation No. 1907/2006, Annex IX, Sect. 9.1., Col. 1 requests the performance of a Long-term toxicity testing on fish, but based on the following reasons, the long-term toxicity testing of fish was considered scientifically not justified based onREACH, Annex XI, Section 1.2 and 1.3:

Exposure and stability considerations:
TBPIN is not stable in the aquatic environment. Due to the unstable nature of organic peroxides, it can be assumed that upon contact with water and organic matter, the test item undergoes rapid degradation resulting in the formation of respective alcohols and acids. Hydrolysis half-life of TBPIN was determined to be 213.2 hrs (ca. 9 days) at 12 °C, reflecting the worst case half-life determined with TBPIN in this study. Therefore, an abiotic degradation of the test item in the environment is expected.
In addition, the test item was found to be readily biodegradable.

Weight of evidence and QSAR:
Based on available data on toxicity to aquatic organisms, algae was considered to be the most sensitive species with the test item.
A long-term toxicity study on Daphnia magna reveiled a 21-d NOEC of 0.22 mg/L, an EC10 of 0.33 mg/L and an EC50 of 0.58 mg/L. These results are a bit higher then the effect levels obtained in the algae inhibition study, wehre a NOEC of 0.125 mg/L was derived after 72 hours of exposure and an EC50 based on growth rate was determined to be 0.51 mg/L. In the short-term test with Daphnia magna no effects were observed up to the limit dose of 100 mg/L (nominal) or 0.518 mg/L (measured concentration). The results obtained in the short-term test on fish show to be quite higher than the results obtained for the other two species - a 96-h LC50 of 7.03 mg/L and a NOEC of 3 mg/L. Therefore, and for animal welfare reasons, long-term toxicity testing with fish is considered to not improve the database and accordingly the chemical safety assessment. This assumption is further supported by QSAR calculations. Chronic toxicity effect concentrations were estimated with ECOSAR v1.11 for algae, daphnia and fish (For more details please refer to IUCLID Section 6.1.2). The test item was within the applicability domain of the model thus reliability of the results is not affected. ChV values were estimated to be 0.117, 0.236 and 0.039 mg/L for fish, daphnia, and algae, respectively, for the chemical group "Peroxyesters", being in well accordance with experimental data for long-term toxicity in algae and daphnia. Based on calculated values, again algae was predicted with QSAR to be the most sensitive species.

Based on the points outline above, long-term toxicity testing is considered scientifically not justified since the test item is not stable in the aquatic environment, the available data shows that the most sensitive species for the aquatic environment has been already determined and the endpoint is adequately covered with a reliable QSAR estimation..

Furthermore, the Environmental Risk Assessment revealed safe use of the substance throughout its whole life cycle due to very low exposure of the water compartment which is especially based on the following facts:
Organic peroxides, when released into the sewage of a plant production or a downstream user’s plant, are treated with other substances in dedicated sewage treatment plants. The activated sludge stemmed from these sewage treatment plants are then extracted and treated as chemical waste. From the production plant, the release of organic peroxide into the sewage is very limited, not to say completely negligible. The waste water from production plant can be treated on site (at least a physical/chemical treatment, which will neutralize potential residual organic peroxide), which is usually followed by a biological treatment. Regarding the rest of the life cycle, organic peroxides are mainly used as cross-linking agent/polymerization initiator for the production of resins/rubbers/polymers. Based upon the fact that organic peroxides are totally consumed during the process (>99%, which is confirmed by the release factor to sewage for curing agents from OECD ESD n°3), the surface water is not exposed to organic peroxides via the waste water system. As a consequence, the surface water and with this aquatic organisms are not considered to be significantly exposed by the test item.
Additionally, TBPIN is used only as an intermediate at industrial setting for the production of other products and reacts completely through the polymerisation process.

In summary, long-term toxicity testing in a vertebrate species is considered not scientifically justified according to REACH Regulation No. 1907/2006, Annex XI, Sect. 1.1. and 1.3, additionally, no further testing based on the chemical safety assessment according to REACH Annex IX, Sect. 9.1., Col. 2 is considered necessary and is not in line with animal welfare.