Reaction Mass of (4R)-4-isopropenyl-1-methylcyclohexene and (4R)-4-(2-methoxypropan-2-yl)-1-methylcyclohexene

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species: fish

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

Guideline:

other: REACH Guidance on (Q)SARs - OECD 305 Bioaccumulation in Fish: Aqueous and Dietary Exposure

Specific details on test material used for the study:

Constituent 1 SMILES: C=C(C)[C@H]1CC=C(C)CC1
Constituent 2 SMILES: COC(C)(C)[C@H]1CC=C(C)CC1
Impurity 1 SMILES: C=CC(=C)CC/C=C(C)\C
Impurity 2 SMILES: CC1=CC=C(C(C)C)CC1
Impurity 3 SMILES: CC1=CCC(C(C)C)=CC1
Impurity 4 SMILES: C/C(C)=C/1CC=C(C)CC1
Impurity 5 SMILES: C=C(C)[C@@H]1CC[C@](C)(OC)CC1
Impurity 6 SMILES: CC1=CC[C@H](C(C)(C)O)CC1
Impurity 7 SMILES: C=C(C)[C@@H]1CC[C@@](C)(OC)CC1
Impurity 8 SMILES: COC1(C)CCC(=C(C)C)CC1
Impurity 9 SMILES: CO[C@@]1(C)CC[C@@H](C(C)(C)OC)CC1
Impurity 10 SMILES: CO[C@]1(C)CC[C@@H](C(C)(C)OC)CC1

Key result

Type:

BCF

Value:

>= 67.79 - <= 432.6 L/kg

Remarks on result:

other: (Q)SAR Prediction

Details on results:

The result is based on bioconcentration (BCF) in fish.

The predictions were generated by the following method using the model. Following classification of the constituent as either ionic or non-ionic; the model applies regression methodology using an appropriate algorithm: by applying fragment contribution and correction factor application where applicable. For non-ionic substances the model then sequentially calculates an estimate the log BCF from the log Kow using:
1. For log Kow – 1.0 to 7.0 the algorithm is as follows:
Log BCF = 0.6598 x log Kow – 0.33 + Σ correction factors
2. For log Kow > 7.0 the algorithm is as follows:
Log BCF = -0.49 x log Kow + 7.554 + Σ correction factors
3. All constituents with a log Kow of less than 1.0 are assigned an estimated log BCF of 0.5.
The full description of the methodology is described in the corresponding QMRF named ‘QMRF Title: BCFBAF v3.01 Bioconcentration Factor (BCF)’ version 1.01; 01 September 2015. There are no transformations of units however anti-logarithmic conversions are made to log BCF predictions to generate the BCF estimates. The result is then compared with the cut-off value given in Regulation (EC) 1272/2008 for classification purposes. The predictions may then also be utilised in other endpoints related to environmental fate and/or toxicological endpoints to better predict the substance’s behaviour. Additional criteria may apply if appropriate when interpreting the result for relevant endpoints.

Descriptors domain:
Falls within the Log Kow domain of > -1.37 (non-ionic) and/or > -6.50 (ionic) and < 11.26 (general domain for the model)
Molecular weight of each constituent is < 959.17 g/mol (non-ionic) and/or < 991.80 (ionic)

Structural Fragment domain:
The substance does not possess functional groups outside those included within the training set of the model. The substance fragments were all assigned from within the model’s library. By expert judgment the model is appropriate to the substance.

Mechanistic domain:
The BCFBAF v3.01 QSAR model as detailed is based on the relationship between octanol/water partition coefficient and the bioconcentration factor of the training set with the incorporation of correction factors. There is no mechanistic basis within the model for prediction of BCF; however it is generally understood that the model and screening criteria for Log Kow relationship with BCF is related to passive diffusion via hydrophobicity driven uptake of the substance. For substances that specifically bind to proteins or surface-active substances where other mechanistic uptake effects occur are considered to be outside the model domain. Expert judgment indicates that these are not relevant for this prediction.

Metabolic domain, if relevant:
Not applicable.

Structural formula and inputs (SMILES) with BCF output of the substance

Constituent Number	CAS RN	Constituent Name (IUPAC)	SMILES Notation	Molecular Weight	Typical Concentration (% w/w)	BCF prediction: BCFBAF L/kg wet-wt
1	5989-27-5	(4R)-4-isopropenyl-1-methylcyclohexene	C=C(C)[C@H]1CC=C(C)CC1	136.23	23.3	360.5
2	30199-25-8	(4R)-4-(2-methoxypropan-2-yl)-1-methylcyclohexene	COC(C)(C)[C@H]1CC=C(C)CC1	168.28	46.2	212.2
Impurity 1	123-35-3	7-methyl-3-methylene-1,6-octadiene	C=CC(=C)CC/C=C(C)\C	136.23	0.5	262
Impurity 2	99-86-5	1-methyl-4-(2-propanyl)-1,3-cyclohexadiene	CC1=CC=C(C(C)C)CC1	136.23	0.5	295.9
Impurity 3	99-85-4	1-methyl-4-(2-propanyl)-1,4-cyclohexadiene	CC1=CCC(C(C)C)=CC1	136.23	0.5	432.6
Impurity 4	586-62-9	1-methyl-4-(2-propanylidene)cyclohexene	C/C(C)=C/1CC=C(C)CC1	136.23	7.7	413.3
Impurity 5	24655-72-9	cis-1-methoxy-1-methyl-4-(1-propen-2-yl)cyclohexane	C=C(C)[C@@H]1CC[C@](C)(OC)CC1	168.28	4	239.1
Impurity 6	10482-56-1	2-[(1S)-4-methyl-3-cyclohexen-1-yl]-2-propanol	CC1=CC[C@H](C(C)(C)O)CC1	154.25	2.7	67.79
Impurity 7	24655-71-8	trans-4-isopropenyl-1-methoxy-1-methylcyclohexane	C=C(C)[C@@H]1CC[C@@](C)(OC)CC1	168.28	1.3	239.1
Impurity 8	1144472-69-4	1-methoxy-1-methyl-4-(2-propanylidene)cyclohexane	COC1(C)CCC(=C(C)C)CC1	168.28	2.4	258.4
Impurity 9	69680-38-2	cis-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	CO[C@@]1(C)CC[C@@H](C(C)(C)OC)CC1	200.32	7.4	71.3
Impurity 10	69680-39-3	trans-1-methoxy-4-(2-methoxypropan-2-yl)-1-methylcyclohexane	CO[C@]1(C)CC[C@@H](C(C)(C)OC)CC1	200.32	1.1	71.3

Validity criteria fulfilled:

not applicable

Conclusions:

The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Since experimental data of high reliability indicates that the substance is not readily biodegradable, calculated Log Kow and the supporting BCF prediction, in conjunction with experimental aquatic acute toxicity data indicate; the substance triggers environmental classification: category chronic 2 under the EU Criteria. Similarly, the results support the conclusion that the substance does not been the bioaccumulative (B) criteria in PBT Assessment.

Executive summary:

A (Q)SAR prediction was used to derive an aquatic BCF (fish), equivalent to an OECD 305 study. The model has been validated with an accompanying QMRF report for the model and a QPRF report for the prediction. The prediction met all relevant criteria to be concluded as fully within the applicability domain of the model. The predictions indicate that the BCF value for all constituents and impurities is significantly <2,000 (BCF range 68 - 433 L/kg). The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Since experimental data of high reliability indicates that the substance is not readily biodegradable, calculated Log Kow and the supporting BCF prediction, in conjunction with experimental aquatic acute toxicity data indicate; the substance triggers environmental classification: category chronic 2 under the EU Criteria.  Similarly, the results support the conclusion that the substance does not been the bioaccumulative (B) criteria in PBT Assessment.

Description of key information

Aquatic BCF (fish) = 67.79 - 432.6 L/kg; (Q)SAR: BCFBAF v3.01 Bioconcentration factor (BCF); Anon. (2017)

Additional information

A (Q)SAR prediction was used to derive an aquatic BCF (fish), equivalent to an OECD 305 study. The model has been validated with an accompanying QMRF report for the model and a QPRF report for the prediction. The prediction met all relevant criteria to be concluded as fully within the applicability domain of the model. The predictions indicate that the BCF value for all constituents and impurities is significantly <2,000 (BCF range 68 - 433 L/kg). The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Since experimental data of high reliability indicates that the substance is not readily biodegradable, calculated Log Kow and the supporting BCF prediction, in conjunction with experimental aquatic acute toxicity data indicate; the substance triggers environmental classification: category chronic 2 under the EU Criteria.  Similarly, the results support the conclusion that the substance does not been the bioaccumulative (B) criteria in PBT Assessment.