Reaction mass of 1-(2,6,6-trimethylcyclohex-2-en-1-yl)hepta-1,6-dien-3-one and 1-(2,6,6-trimethylcyclohex-1-en-1-yl)hepta-1,6-dien-3-one

Endpoint summary

Description of key information

For Hexalon the following results were derived:

Guideline	Test species	Endpoint	Result	Remark
OECD TG 203	Cyprinus carpio	96-h LC50	4.1 mg/l	Data derived from read-across to Galbascone (CAS# 56973 -85 -4). Semi-static conditions and measured concentrations were used. Key study, rel. 1.
OECD TG 202	Daphnia magna	48-h EC50	3.4 mg/l	Data derived from read-across to Galbascone (CAS# 56973 -85 -4). Static conditions and measured concentrations were used. Key study, rel. 1.
OECD TG 201	Pseudokirchneriella subcapitata	72-h ErC50 72-h ErC10 72-h NOErC	5.3 mg/l 2.0 mg/l 1.1 mg/l	Data derived from read-across to Galbascone (CAS# 5673 -85 -4). Static conditions and measured concentrations were used. Key study, rel. 1.
OECD TG 301F	Activated sludge, domestic	28 -d NOEC	35 mg/l	Readily biodegradable at a test concentration of 35 mg/l. Key study, rel. 1.

Additional information

The aquatic toxicity of Hexalon is based on read across from Galbascone. The read across documentation is for algae, Daphnia and fish and is therefore included in the Endpoint summary of Aquatic toxicity. The accompanying files are also attached in this Endpoint summary.

The read across justification is presented below:

Aquatic toxicity of Hexalon (CAS #79-78-7) based on read across from Galbascone (CAS #56973-85-4)

Introduction and hypothesis for the analogue approach

Hexalon (CAS #79-78-7) has a trimethyl-cyclohexene ring with an alkyl chain to it. The alkyl chain has an alpha-beta conjugated ketone bond (also called a vinyl/allyl group) and has an allyl bond at the end of the chain.For this substance no aquatic toxicity information is available.

In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the aquatic toxicity of Hexalon the analogue approach is selected because for a closely related analogue, Galbasconeaquatic toxicityinformation is available which can be used for read across.

Hypothesis: Hexalon has similar aquatic toxicity potential as Galbascone asboth substances are vinyl/allyl ketones and therefore the octanol-water partitioning coefficients (log Kow) are considered to give direct indication of their toxicities.

Available information: For the source chemical Galbasconedata are available from GLP guideline studies with fish, aquatic invertebrates and aquatic algae.Short-term effect values for Galbascone were determined to be in the range of 1-10 mg/L for fish, Daphnia, and algae. EC10 and NOEC values in the algae study were >1 mg/L. All tests are according to current OECD guidelines and have a reliability of 1.

In more detail: For Galbascone, short-term fish study was performed according to OECD TG (203 and GLP, WILRES, 2015). The 96-h LC50 value is 5.0 mg/L in common carp (C. carpio). An aquatic invertebrates study was performed according to OECD TG 202 and GLP, WILRES, 2015). The 48-h EC50 is 4.2 mg/L inDaphnia magna. The data are reliable without restrictions (Klimisch 1). Finally, a freshwater algae study was performed according to OECD TG 201 and GLP, WILRES, 2016). The 72-h ErC50, ErC10 and NOEC values are 6.5 mg/L, 2.4 mg/L and 1.3 mg/L, respectively in green algae (P. subcapitata).

Target chemical and source chemical(s)

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

Purity / Impurities

Hexalon contains one main constituent present at ca. 78%, a constituent present at ca. 10% and three additional constituents all present below 5%. Except one (1.3%) all minor constituents of Hexalon have similar structures: a ring with an alkyl chain with a ketone group. This minor one has more a ring type of structure instead of a chain which is not expected to have a more severe aquatic toxicity compared to the other constituents. Galbascone contains two constituents that are isomers. As a result it is not expected that the impurities of the source and target chemicals affect the read-across justification.

Analogue approach justification

According to Annex XI section 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. Galbascone was selected for read across because it was the most similar substance when compared to other ionones/damascones such as presented in Belsito et al., 2007. The ECHA guidance (2017) has been considered when appropriate.

Structural similarities and differences:Hexalon has a trimethyl-cyclohexene backbone with an alkyl chain attached to it. The functional group is the alpha-beta conjugated ketone group also referred to as (vinyl/allyl ketone group). At the end of the alkyl chain there is an allyl bond which is not considered to be very reactive as such. Galbascone has a somewhat similar backbone, similar functional group and also an allyl group at the end of the alkyl chain. The difference is that Hexalon has this vinyl/allyl ketone bond just outside the ring while Galbascone has it inside the ring. This is expected not to influence the reactivity because both functional groups are slightly hindered by the ring structure: Galbascone having the group in the ring and Hexalon has this group just outside the ring.

Bioavailability: The molecular weights and the structure of both substances indicate that these substances will be bioavailable. The difference in log Kow is expected to present a direct relation of their toxicity: 5.5 for Hexalon and 4.5 for Galbascone.

Reactivity: Hexalon and Galbascone are expected to have the same reactivity because these substances have identical vinyl/allyl ketone chains with a similar backbone. This backbone is non-specific with respect to ecotoxicity; the contribution to reactivity will be reflected in their contribution to the overall log Kow values of the respective substances.

Conversion of the short -term values to Hexalon from Galbascone:The difference in log Kow between Hexalon and Galbascone will be used for conversion of the toxicity values as follows: Effect value Hexalon in mg/L = (Effect value of Galbascone in mg/L x (log Kow Galbascone/Log Kow Hexalon)).

Uncertainty of the prediction:There is no remaining uncertainty because the aquatic toxicity values of Galbascone were corrected to present the expected higher toxicity for Hexalon based on the higher log Kow of the latter substance. Altogether, Hexalon will present a slightly lower toxicity (higher effect values) based on its higher molecular weight which is counterbalanced by its slightly higher log Kow.

Conclusions for hazard assessment, C&L, PBT and risk characterisation

For Hexalon no experimental aquatic toxicity information is available. Read-across is performed to the structural analogue Galbascone. After correction for difference in molecular weight and log Kow, the lowest short-term effect value is 3.4 mg/L in Daphnia. Long-term data is available only from the algae study from which an EC10 of 2.0 mg/L was derived (also after correction for log Kow). These values will be taken forward to the risk assessment.

Data matrix presenting the ecotoxicological information to read across for Hexalon from Galbascone

Common name	Hexalon	Galbascone
Chemical structures
Chemical name	1-(2,6,6-trimethyl-2-cyclohexen-1-yl)hepta-1,6-dien-3-one	1-(5,5-dimethyl-1-cyclohexen-1-yl)pent-4-en-1-one
REACH registration	2018	2018
CAS no	79-78-7	56973-85-4
EINECS	201-225-9	260-486-7
Smiles	O=C(C=CC(C(=CCC1)C)C1(C)C)CCC=C	CC1(C)CC(=CCC1)C(=O)CCC=C
Empirical formula	C16H24O	C13H20O
Molecular weight	232.4	192.3
Physical state	Liquid	Liquid
Melting point	-20 °C	-20 °C
Boiling point	301.1 °C	265.8 °C
Vapour pressure	0.08 Pa (at 24 °C)	1.14 Pa(at 23 °C)
Water solubility	79.0 mg/L           (at 24 °C)	88.9 mg/L            (at 22 °C)
Log Kow	5.5                        (at 24 °C)	4.5                         (at 25 °C)
Aquatic toxicity
Fish LC50 in mg/L	Read across from Galbascone: 4.1 (= 5.0 mg/L x 4.5/5.5 (log Kow))	5.0
Aquatic invertebrates EC50 in mg/L	Read across from Galbascone: 3.4 (=4.2 mg/Lx 4.5/5.5 (log Kow))	4.2
Aquatic algae 72-h ErC50 in mg/L 72-h ErC10 in mg/L 72-h NOEC in mg/L	Read across from Galbascone: 5.3 (=6.5 mg/Lx 4.5/5.5 (log Kow)) 2.0 (=2.4 mg/Lx 4.5/5.5 (log Kow)) 1.1 (=1.3 mg/Lx 4.5/5.5 (log Kow))	6.5 2.4 1.3