Reaction mass of (3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulen-6-yl rel-acetate and rel-(1aR,4aR,8aR)-2,4a,8,8-tetramethyl-1,1a,4,4a,5,6,7,8-octahydrocyclopropa[d]naphthalene and rel-(3R,3aS,7S,8aS)-3,6,8,8-tetramethyl-2,3,4,7,8,8a-hexahydro-1H-3a,7-methanoazulene

Endpoint summary

Description of key information

For Cedryl Acetate EOA the following results were derived:

Species	Guideline / Method	Result	Remarks
Daphnia magna	Read across	48-h EC50: 0.2 mg/L	Key study, Rel. 2. Value derived from read-across to Longifolene Coeur   (CAS# 475-20-7, tested in an OECD TG 202)
Algae	Read across	72-h ErC50: 0.28 mg/L 72-h ErC10: 0.15 mg/L	Key study, Rel. 2. Value derived from read-across to Longifolene Coeur (CAS# 475-20-7, results derived from ECOSAR)

Additional information

The aquatic toxicity is assessed based on read-across from Cedryl Acetate 'mono) and Longifolene Coeur to Cedryl Acetate EOA. The executive summary of the source information is presented in the respective Endpoint summaries. The read-across rationale is presented below.

Aquatic toxicity of Cedryl Acetate EOA based on read across from data available forCedryl Acetate ‘mono’ (CAS#77-54-3) and Longifolene Coeur (CAS# 475-20-7).

 

Introduction and hypothesis for the analogue approach

Cedryl acetate EOA consists of one major, two minor constituents and a number of impurities, all containing a hydrocarbon fused-ring system.Half of the constituents have an acetate attached to this ring the other half does not have this ester group. Most constituents have a double bond with a methyl group attached. The constituents are sub-grouped into two main types: Cedryl acetate-type and Longifolene Coeur-type (hydrocarbon-fused-ring-type).

ForCedryl Acetate EOAthere are no experimentalaquatic toxicitydata available.In accordance with Article 13 of REACH, lacking information can be generated by means other than experimental testing, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.For assessing theaquatic toxicityofCedryl Acetate EOA, the analogue approach is selected because for the main constituent, Cedryl acetate ‘mono’, and for the close structural analogue Longifolene Coeur, aquatic toxicitydata isavailable which can be used for read across.

Hypothesis: Cedryl Acetate EOA has the same aquatic toxicity as Cedryl Acetate ‘mono’ and Longifolene Coeur.

Available information:For Cedryl acetate ‘mono’data are available from GLP guideline studies with aquatic invertebrates and aquatic algae. For Longifolene Coeur, acute toxicity data to daphnids is available from a GLP guideline study. For the algae toxicity of Longifolene Coeur, data is available from reliable QSAR predictions (ECOSAR).Short-term effect values forCedryl acetate (‘mono’) and Longifolene Coeurwere determined to be in the range of 0.1 - 1.0 mg/L for both Daphnia and algae. The chronic effect value for algae is also in the range of 0.1 - 1.0 mg/L.

In more detail Daphnia:

For Cedryl Acetate ‘mono’a Daphnia study was performed according to OECD TG 202 and in compliance with GLP. In this semi-static study, Daphnia were exposed to WAFs prepared at loading rates of 2.2, 4.6, 10, 22 and 46 mg/L. The 48-h EC50 was determined at 0.33 mg/L, based on geometric mean measured concentrations. The data is assignedreliable without restrictions (Rel. 1).

For Longifolene Coeur, a Daphnia study was performed according to OECD TG 202 and in compliance with GLP. In this semi-static study, Daphnia were exposed to WAFs prepared with a nominal loading rate of 300 mg/L and dilutions at 1:2, 1:4, 1:8 and 1:16. The 48-h EC50 was determined at 0.119 mg/L based on geometric mean measured concentrations. The data is assigned reliable without restrictions (Rel. 1).

Algae, for Cedryl Acetate ‘mono’an algae study was performed according to OECD TG 201 and in compliance with GLP. In this study, algae were exposed to WAFs prepared at loading rates of 0.10, 0.40, 1.6, 6.4, 26 and 100 mg/L. No robust NOEC and ECx-values could be determined for both growth rate and yield due to the fact that no dose-response curve could be obtained with the geometric measured concentrations. However, it can be safely stated that the ErC50 was > 0.31 mg/L due to the effect not exceeding 50% at this highest tested measured concentration. The data is assigned reliable without restrictions (Rel. 1).

For Longifolene Coeuralgae toxicity data are generated by means of QSAR (ECOSAR). The calculated 72-h ErC50 and ErC10 values are 0.28 and 0.15 mg/L, respectively. The data is assigned Rel. 2 for a QSAR with adequate and reliable documentation/justification.

In summary: The overall lowest acute effect value is 0.119 mg/L as observed in the Daphnia study for Longifolene Coeur. The lowest chronic effect value is 0.15 mg/L as calculated in ECOSAR for Longifolene Coeur.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical(s) are shown in the data matrix, including physico-chemical properties and available ecotoxicological information.

Purity / Impurities

The unidentified impurities of Cedryl Acetate EOA are not considered to have a significant influence on the aquatic toxicity.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation, which is presented below.

Analogue selection:. The representatives of both sub-groups were selected as analogues for the following reasons:Cedryl Acetate ‘mono’ and Longifolene Coeurwere selected as source chemicals for read-across as they are considered representatives for two sub-groups of constituents of Cedryl Acetate EOA, based on their structures and functional groups.

Structural similarities and differences:Cedryl Acetate EOA components (constituents and impurities) all have a hydrocarbon fused-ring system similar to Cedryl Acetate ‘mono’ and Longifolene Coeur. All components are multi-methylated with 3-5 methyl groups attached at varying positions. The first analogue has an ester functionality, which is absent in the second one.

Bioavailability: Bioavailability will be similar between the Cedryl acetate EOA components in view of log Kow of >=5.

Reactivity:Cedryl Acetate-type constituents belong to the toxicity class ‘esters’ whereas the Longifolene Coeur type (solely hydrocarbon-fused-ring-type) belong to the toxicity class neutral organics. The ester type can be considered slightly more reactive. At high log Kows (around 5) such differences become small and therefore all components are considered similar reactive. This is supported with the experimental information for both substances, which have acute toxicity values for algae and Daphnia between 0.1 and 1 mg/l.

Conversion of the effect values from Cedryl Acetate ‘mono’ and Longifolene Coeur to Cedryl Acetate EOA as a whole:No log Kow correction needs to be performed. The estimated log Kow values of all constituents and the structural analogue range from ca. 5.3 to 6.2. This range is comparable to differences between estimated and experimental log Kow values obtained for Cedryl Acetate ‘mono’ (0.7 underestimation of log Kow) and Longifolene Coeur (0.5 overestimation of log Kow). Also, no molecular weight correction will be performed as molecular weights are identical for all constituents per each sub-group.

Uncertainty of the prediction: There are no uncertainties other than those already discussed above.

Data matrix

The relevant information on physico-chemical properties and ecotoxicological characteristics are presented in the data matrix below.

Conclusions for environmental assessment

ForCedryl Acetate EOAno experimental aquatic toxicity information is available and read across is used to fill this gap. Read-across can be used when the approach is adequately and reliably document. The current text is fulfilling the documentation. Two analogues are found: Cedryl Acetate ‘mono’ and Longifolene Coeur which are representatives for the two sub-groups of constituents in Cedryl Acetate EOA.The lowestshort-term effect value was found for Longifolene Coeur is 0.12 mg/l (Daphnia). The one algae EC10 value was found for Longifolene Coeur being 0.15 mg/l.

Final conclusion: Cedryl Acetate EOA has an EC50 Daphnia toxicity of 0.12 mg/l, EC50 and EC10 for algae is 0.28 and 0.15 mg/l, respectively.

 

Data matrix to support the read across to Cedryl acetate EOA from Cedryl acetate and Longifolene Coeur for aquatic toxicity

Common names	Cedryl Acetate EOA							Cedryl acetate	Longifolene Coeur
	Target	Target	Target	Target	Target	Target	Target	Source	Supporting source
	Cedryl Acetate type			Longifolene type
Chemical structures
Typical concentration (%)	30-45 (major)	<10	<10	15-30 (minor)	8-16 (minor)	<10	<10
CAS no				32435-95-3	22567-43-7			77-54-3	475-20-7
Einecs	944-520-4							201-036-1	207-491-2
REACH	2018	2018						2018	2018
Smiles								O=C(OC(C(CC(C1CC2) (C2C)C3)C1(C)C)(C3)C)C	C(C(C(C1=C)C2)C(CCC3) (C)C)(C13C)C2
Molecular weight	264	264	264	204	204	204	202	264	204
Phys-Chem data*
Log Kow	5.33	5.33	5.94	6.12	5.74	5.82	6.19	5.33 (6 exp.)	5.48 (5 exp.)
Ecotoxicity
Acute Daphnia mg/l	0.119 (Read across)	0.119 (Read across)	0.119 (Read across)	0.119 (Read across)	0.119 (Read across)	0.119 (RA)	0.119 (RA)	0.3 (OECD TG 202)	0.119 (OECD TG 202)
Algae EC50 EC10 mg/l	0.28 0.15 (Read across)	0.28 0.15 (Read across)	0.28 0.15 (Read across)	0.28 0.15 (Read across)	0.28 0.15 (Read across)	0.28 0.15 (RA)	0.28 0.15 (RA)	> 0.31 Not reportable (OECD TG 201)	0.28 0.15 (ECOSAR)

*Physico-chemical properties are calculated with EpiSuite; RA=Read across