Reaction mass of (4R)-4-(2-methoxypropan-2-yl)-1-methylcyclohexene and cis-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2016

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

Guideline:

other: REACH guidance on QSARs R.6, OECD Guideline 202 (Acute Daphnia sp. Immobilisation Test), with modifications from OECD Series on Testing and Assessment no. 23 on ecotoxicity testing of difficult substances.

Principles of method if other than guideline:

The QSAR method was validated using data from tests preformed using the OECD document 23 recommnedations for poorly water soluble complex mixtures. The QSAR is thus validated ot be compliant inline with such methods/recommendations.

Specific details on test material used for the study:

SMILES: N/A.

The substance is a mixture. The toxicity is, therefore, based on seperately determined QSAR endpoints for each constiuent. Please refer to the study reports, QSAR of the acute toxicity of (4R)-4-(2-methoxy-2-propanyl)-1-methylcyclohexene to Daphnia, QSAR of the acute 1-methoxy-1-methyl-4 -(2-propanylidene)cyclohexane toxicity to Daphnia, QSAR of the acute toxicity of 1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane to Daphnia and QSAR of the acute toxicity of 2-[(1S)-4-methyl-3-cyclohexen-1-yl]-2-propanol to Daphnia for individual constiuent SMILES.

Key result

Duration:

48 h

Dose descriptor:

EL50

Effect conc.:

30 mg/L

Remarks on result:

other: QSAR predicted value.

Details on results:

This approach uses a thermodynamically based module to calculate the water concentrations and the individual toxicity of each of the constituent is first derived from a QSAR model validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). Then the effective loading rate of the mixture to the test organisms (i.e. Daphnia magna) is determined as a Water Accommodated Fraction (WAF) test (OECD, 2000).

The overall validity of the approach depends on the validity of the input endpoints. All endpoints estimated for each constituent were within the applicability domain of the QSAR used. Therefore, the overall EL50 predicted for Daphnia is conisdered relaible.

Results with reference substance (positive control):

N/A

Reported statistics and error estimates:

N/A

Ecotoxicity endpoint values to Daphnia magna(48h-EC50) used within the calculation method to determine WAF aquatic toxicity to Daphnia magna.

constituents	48h-EC50 (mg.L^-1) used
(4R)-4-(2-methoxy-2-propanyl)-1-methylcyclohexene	10
cis-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	163
cis-1-methoxy-1-methyl-4-(2-propanylidene)cyclohexane	9.8
2-[(1S)-4-methyl-3-cyclohexen-1-yl]-2-propanol	61
trans-1-methoxy-1-methyl-4-(1-propen-2-yl)cyclohexane	9.8
1-methoxy-1-methyl-4-(2-propanylidene)cyclohexane	12
trans-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	163

Concentration of each constituent in the WAF of the test substance at 30 mg/L (i.e. the EL50)

constituents	concentration in the WAF (mg.L^-1)
(4R)-4-(2-methoxy-2-propanyl)-1-methylcyclohexene	21
cis-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	3.1
cis-1-methoxy-1-methyl-4-(2-propanylidene)cyclohexane	1.4
2-[(1S)-4-methyl-3-cyclohexen-1-yl]-2-propanol	0.68
trans-1-methoxy-1-methyl-4-(1-propen-2-yl)cyclohexane	0.53
1-methoxy-1-methyl-4-(2-propanylidene)cyclohexane	1.1
trans-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	0.44

Conclusions:

The 48 hour EL50 to Daphnia sp. of the reaction mass of (4R)-4-(2-methoxypropan-2-yl)-1-methylcyclohexene and cis-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane , estimatedfrom the iSafeRat v.2.2 QSAR inputs from each constieunt and, calculations based on thermodynamics of each constituent and there eventual contribution to the toxicity was 30 mg/L. The endpoint value is considered valid for use in risk assessment (including PBT assessment) and classification and labelling. The prediction is adequate as contributing data for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3.

Executive summary:

This approach uses a thermodynamically based module to calculate the water concentrations and the individual toxicity of each of the constituent is first derived from a QSAR model validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). Then the effective loading rate of the mixture to the test organisms (i.e. Daphnia magna) is determined as a Water Accommodated Fraction (WAF) test (OECD, 2000).

The inputs into the model all came from reliable QSAR estimations. The endpoint value is considered valid for use in risk assessment (including PBT assessment) and classification and labelling. The prediction is adequate as contributing data for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3.

The 48 hour EL50 for the test substance was estimated to be 30 mg/L.

Description of key information

48 h EL50 30 mg/L, REACH guidance on QSARs R.6, OECD Guideline 202 (Acute Daphnia sp. Immobilisation Test), with modifications from OECD Series on Testing and Assessment no. 23 on ecotoxicity testing of difficult substances, Thomas 2016.

A supporting study on the acute toxicity of the substance to Daphnia magna was also conducted in accordance with OECD 202 (Anon. 2017). The EL50 was determined following 48h exposure of daphnids to water accommodated fractions of the test item, thus creating the conditions under which the key (Q)SAR predictions were made. The resulting 48h EL50 was estimated as 9.84 mg/L (95 % CI: 9.16 -10.7). The results of this study support the magnitude of the key effect levels generated by each (Q)SAR study for Daphnia and alge, providing further evidence of their relevance and reliability for these endpoints.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

30 mg/L