α-methyl-1,3-benzodioxole-5-propionaldehyde

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

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:

According to Annex XI, paragraph 1.3 results obtained from QSAR models may be used instead of testing when the following conditions are met:
- results are derived from a QSAR model whose scientific validity has been established: See attached QMRF
- the substance falls within the applicability domain of the QSAR model: See attached QPRF
- results are adequat for the purpose of classification and labelling and/or risk assessment: yes
- adequate and reliable documentation fo the applied method is provided: See attached QMRF & QPRF

Reference 2

Endpoint:

fish early-life stage toxicity

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2022

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:

For detailed description of the model and its applicability domain, see attached QMRF and QPRF document.

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 2.0 for chemical class "Aldehydes (Mono)"

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC(Cc1ccc2OCOc2c1)C=O

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.:

0.87 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Aldehydes (Mono)".

Organism	Duration	Endpoint	Concentration (mg/L)	Max Log Kow	Flags
Fish	96h	LC50	7.54	5
Daphnid	48h	LC50	6.61	5
Green Algae	96h	EC50	4.07	6.4
Fish		ChV	0.87	8
Daphnid		ChV	0.08	8
Green Algae		ChV	1.71	8

Validity criteria fulfilled:

yes

Conclusions:

Using ECOSAR v2.0 the long-term toxicity ChV value for fish was calculated to be 0.87 mg/L. The substance is within the applicability domain of the model.

Executive summary:

The long-term toxicity in fish was calculated using ECOSAR v2.0 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.

Description of key information

According to Annex XI, paragraph 1.3 results obtained from valid QSAR models may be used instead of testing. A QSAR calculation is available for this endpoint showing that the substance is not chronic toxic to fish.

Based on the results of the QSAR calculation for the long-term toxicity to fish,  the information from the short-term aquatic toxicity tests with fish, daphnia and algae and the information from the chronic algae and daphnia tests - it can be shown that the substance is not aquatic toxic. Thus, to avoid unnecessary testing on vertebrate animals no additional test on long-term toxicity to fish is needed to be able to conclude on the non-toxicity of the substance for aquatic organisms.

Furthermore, this is supported by the good solubility in water (934000 mg/L) and the low bioaccumulation potential (log Kow = 2.4). For further justification, please refer to 'Additional information'.

Additional information

Long-term toxicity testing on fish (Annex IX, Section 9.1.6.; test method: EU C.47./OECD TG 210)

The Registrant adapts the information requirements under Annex IX of REACH with regard to long-term toxicity testing on fish in accordance with Annex XI, Section 1.3 by providing the requested information using an appropriate QSAR method. Additionally, an Expert Judgement was performed in order to support the evidence that the substance is not expected to be chronically harmful to fish. A robust study summary of the QSAR estimation and the Expert Judgement is provided below.

 

QSAR data on long-term toxicity to fish

The long-term toxicity on fish has been assessed using ECOSAR v2.0 (US Environmental Protection Agency). The long-term toxicity value for fish was calculated to be 0.87 mg/L, showing that the substance is not chronic toxic to fish. The substance is within the applicability domain of the model.

 

Expert Judgement

The structure as well as the physico-chemical properties of the Substance are clearly identified. The substance was shown to be not rapidly, but inherently biodegradable (Rudio, 1998; Desmares-Koopmans, 2002). However, it is regarded as being potentially persistent (P) or very persistent (vP) according to the ECHA Guidance on PBT/vPvB assessment (2017). Based on the log Kow value of 2.4 the substance has no potential for bioaccumulation, therefore uptake via the food chain is not of concern. Even though none of the endpoints for aquatic ecotoxicity (NOEC, EC50, LC50 and EC10) are < 0.1 mg/L (the trigger value for toxicity (T)), α-methyl-1,3-benzodioxole-5-propionaldehyde (HLF) does fulfil the toxicity (T) criteria as it is classified as toxic for reproduction (category 2, H361). It is classified for chronic aquatic toxicity into Category 2 (H411) according to  Regulation (EC) No 1272/2008. This classification is triggered by the absence of chronic toxicity data in combination with the substance being not readily biodegradable.

QSAR predictions for long-term toxicity to aquatic invertebrates and fish are available for the substance. The long-term toxicity to daphnia was calculated using ECOSAR v2.0 from US Environmental Protection Agency as well. The long-term toxicity  value for daphnids was calculated to be 0.08 mg/L.

The available short-term toxicity data for the three trophic levels (fish, aquatic invertebrates and algae) do not indicate a concern for a high sensitivity of fish, as summarised below:

_{Table 1. Key results from short-term toxicity aquatic tests}

Test organism	Key result [mg/L]	Test Guidance	Reference
Fish (Oncorhynchus mykiss)	96 h LC50 = 5.3	OECD 203	Parr, 2015
Aquatic invertebrates (Daphnia magna)	EC50 = 8.3	OECD 202	Lenertz, 2001
Algae (Pseudokirchneriella subcapitata)	EC50 = 28 NOEC = 6.25	OECD 201	Vryenhoef, 2013

 

Taken together, the intrinsic properties of the substance indicate that significant and relevant long-term effects on fish are not expected to occur. The substance has no specific mode of action and does not produce structural alerts for relevant effects.

Overall, the available data on the substance’s toxicity and properties together with a QSAR prediction sufficiently support the conclusion that the substance does not have a particular dangerous or harmful property to fish, in line with Annex XI, Section 1.3 of Regulation (EC) No 1907/2006.

The QSAR prediction and the Expert judgement data contain all relevant information required according to Annex IX, Section 9.1.6, column 1. The Registrant will not perform a long-term toxicity test on fish. Further testing does not seem justified and long-term toxicity testing on fish should therefore not be carried out to avoid unnecessary testing on vertebrate animals. Avoiding unnecessary testing of vertebrate animals is also in line with the REACH regulation, which states in §25 that testing on vertebrate animals shall be undertaken as a last resort. This is further supported by the EU Directive on the protection of animals used for scientific purposes (Directive 2010/63/EU, of 22 September 2010) and the EURL ECVAM strategy to replace, reduce and refine the use of fish in aquatic toxicity and bioaccumulation testing (EURL ECVAM, 2014).

 

 

References

ECHA (2017). Guidance on Information Requirements and Chemical Safety Assessment Chapter R.11: PBT/vPvB assessment. Version 3.0, June 2017. ECHA-17-G-12-EN.

EURL ECVAM (2014). Prieto Peraita M, Burton J, Graepel R, Price A, Whelan M, Worth A. EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity. EUR 26704. Luxembourg (Luxembourg): Publications Office of the European Union; 2014. JRC90611.