Octahydro-4,7-methano-1H-inden-5-yl acetate

Endpoint summary

Description of key information

Chronic aquatic toxicity data for three trophic levels for Cyclacet Dihydro show values > 1 mg/l using read across to Cyclacet (Algae) and acute / chronic ratios from Cyclaprop (Daphnia and fish).

Additional information

In the table below the acute and long-term toxicity for Cyclacet Dihydro is derived from Cyclacet and the acute / chronic ratio for each species from Cyclaprop. Thereafter the read across justification is presented.

Species	Endpoint	Method	Result in mg/l	Comments
Fish	Acute toxicity	RA from Cyclacet (OECD TG 203)	LC50: 15.8	Reliability 1 for Cyclacet test
	Acute toxicity		LC50: 6.7	Reliability 1 Cyclaprop test (OECD TG 203)
	Long term toxicity	A/C ratio derived from acute and chronic toxicity data of Cyclaprop (OECD TG 202 and 210)	EC10: 1.9	Reliability 2 because of using A/C ratio. Cyclaprop test has Reliability 1
Daphnia	Acute toxicity	RA from Cyclacet (OECD TG 202)	25	Reliability 1 for Cyclacet test
	Acute toxicity		EC50: > 14	Reliability 1 Cyclaprop test (OECD TG 202)
	Long-term toxicity	A/C ratio derived from acute and chronic toxicity data of Cyclaprop OECD TG 211	1.8	Reliability 2 because of using A/C ratio. Cyclaprop test has Reliability 1
Algae	Acute toxicity	RA from Cyclacet (OECD TG 201)	25	Reliability 1 for Cyclacet test
	Long-term toxicity	A/C ratio derived from acute and chronic toxicity data of Cyclaprop (OECD TG 201)	3.2	Reliability 1 for Cyclacet test
Micro-organism	Acute toxicity	RA from Cyclacet (OECD TG 209)	245	Reliability 1 for Cyclacet test
	Long term toxicity	RA from Cyclacet OECD TG 209)	53	Reliability 1 for Cyclacet test

Cyclacet Dihydro and its aquatic toxicity using read across information from Cyclacet and other Cycla-esters

Introduction and hypothesis for the analogue approach

Cyclacet Dihydro has a tricyclodecane fused ring structure with an acetic ester attached to it for which no aquatic toxicity information is available. In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such asin vitrotests, QSARs, grouping and read-across. For assessing the acute aquatic toxicity of Cyclacet the analogue approach is selected because for a group of closely related esters acute and chronic information is available.

Hypothesis: Cyclacet Dihydro has the same acute aquatic toxicity and the same long-term toxicity for algae and micro-organisms as Cyclacet. For deriving the long-term Daphnia and fish toxicity the acute/chronic ratio of Cyclaprop is used, which is applied to the acute Daphnia and fish toxicity values of Cyclacet. 

Available experimental information: There is no experimental aquatic toxicity for Cyclacet Dihydro. For Cyclacet reliable acute algae, Daphnia, fish and micro-organism toxicity data are available according to current guidelines and all receive Reliability 1. For Cyclacet there is a chronic value for algae and micro-organisms. For Cyclaprop there is chronic information on Daphnia and fish. This chronic information is also derived from experimental testing according to current guidelines and all studies receive reliability 1. The toxicity values can be found in the data matrix at the end.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix. Also physico-chemical properties thought relevant for aquatic toxicity are listed in there

Purity / Impurities

The purity, the constituents and impurities of the target substance do indicate a similar aquatic toxic potential. The impurities are all below < 10%.

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.

In accordance with ECHA guidance (2017, RAAF), Cyclacet and Cyclaprop have been selected in view of the close analogy one double bond and one addition methyl-group and a double bond, respectively.

Structural similarities and differences:The Cyclacet Dihydro and Cyclacetboth have a tricyclodec- a/e nyl-fused ring structure with an acetic ester attached to the bridged hexyl-ring. Cyclaprop has a propyl ester attached to this fused-ring structure. The difference with Cyclacet is the missing of the double bond in the pentyl-ring (as presented in the name of Cyclacet Dihydro). The difference with Cyclaprop is the missing of the double bond in the pentyl ring and the attached ester is a propyl one instead of an acetic one. This means that both the backbone and the functional groups are very similar.

Bioavailability:Cyclacet Dihydro and Cyclacet have verysimilar bioavailability based on the similarity in chemical structure and physico-chemical properties. The molecular weight of both substances is 194 versus 192. They are both liquids, have very similar measured vapour pressures (2.2 and 2.1 Pa) and water solubilities (89 and 186 mg/l, they also have the same calculated log Kow. The measured log Kow of Cyclacet Dihydro is slightly higher (4.5) compared to Cyclacet (3.9) but is anticipated to be due to the experimental variability (the calculated values show that Cyclacet Dihydro (3.1) has only a slightly higher value compared to Cyclacet (2.85). Overall, the bioavailability and the aquatic toxicity profile of the target and the source substances will be similar.

Mode of Action and the prediction of the chronic information:Cyclacet Dihydro has the same mode of action as the other Cycla-esters. Their similar backbone and their similar functional group, being an ester, will present a similar mode of action. This same mode of action has resulted in an incremental decrease of acute LC and EC50 values for fish and Daphnia based on the increased alkyl chain from Cyclacet onwards (see data matrix).

Acute aquatic toxicity: For the prediction of acute aquatic toxicity for Cyclacet Dihydro the experimentally data from Cyclacet are used.

Chronic aquatic toxicity: For prediction of the chronic toxicity of Cyclacet Dihydro for algae and micro-organisms the result from Cyclacet will be used.

For predicting Cyclacet Dihydro’s chronic toxicity of Daphnia and fish the acute / chronic ratio of Cyclaprop will be used. This reflects the toxicity best because a) experimental data are used; b) it reflects the difference in toxicity of the shorter and longer alkyl chain; and c) the approach is applied separately for fish and Daphnia.

Fish: The key information is the experimental Cyclaprop A/C ratio of 8.4 for fish, which results in a Cyclacet Dihydro value of 1.9 ( 15.8 (mg/l) / 8.4 (A/C ratio). This value will be used for the risk assessment.

Daphnia: The key information is the experimental A/C ratio for Daphnia of 14 for Cyclaprop, which results in a Cyclacet Dihydro EC10/NOEC of 1.8 mg/l (25 (mg/l) / 14). This 1.8 mg/l will be used for the risk assessment.

Uncertainty of the predictions: For acute aquatic toxicity there is a high certainty for the read across between from Cyclacet Dihydro and Cyclacet in view of their similaritiesconsidering the structure, the physico-chemical properties and the mode of action.The A/C ratios for the different trophic levels for Cyclacet Dihydro based on Cyclaprop have a high certainty because of close similarity between these two substances considering the structure, the physico-chemical properties and the mode of action. Therefore the alkyl chain length will not have an impact on the A/C ratio and thus the A/C ratio of Cyclaprop can be used to present the chronic toxicity of Cyclacet.

In view of the reasoning and using the criteria of the ECHA guidance (2017, RAAF) the read across receives a quality code of 5.

Data matrix:The data matrix is presented at the end of this section.

Conclusions on hazard and Classification and labelling

For Cyclacet Dihydro acute aquatic toxicity information is used from Cyclacet and for chronic aquatic toxicity for algae and micro-organisms Cyclacet is used. For chronic toxicity the acute / chronic (A/C) ratio from Cyclaprop is applied. Acute algae, Daphnia and fish toxicity for Cyclacet are 15.8, 25 and 25 mg/l and therefore also Cyclacet Dihydro will have the same toxicity values. For Cyclacet for chronic algae toxicity the EC10/NOEC is 3.2 mg/l and for micro-organisms it is 53 mg/l. The derived chronic data for fish and Daphnia for Cyclacet Dihydro are the same as for Cyclacet , 1.9 and 1.8 mg/l based on the A/C ratio derived from Cyclaprop.

Final conclusion on classification and labelling: For Cyclacet Dihydro 3 chronic aquatic toxicity values are derived all being > 1mg/l and therefore the substance does not need to be classified for aquatic toxicity.

 

Data matrixof Cyclacet Dihydro and the related Cycla-esters for aquatic toxicity is presented below. The matrix is ordered from shortest alkyl chain to the longer ones. The bold values are experimental values, the italic one are derived values.                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

Common names	Cyclacet Dihydro	Cyclacet	Cyclaprop
Chemical structures
	Target	Source	Source
Cas no of the main isomer Cas no of the generic	64001-15-6	2500-83-6 (5-yl) 54830-99-8 C12H16O2	- 68912-13-0 C13H18O2
Smiles	O=C(OC(C(C(C(C12)CC3)C3)C1)C2)C	CC(=O)OC3CC1CC3C2CC=CC12	CCC(=O)OC3CC1CC3C2CC=CC12
Physico-chemical data
Molecular weight	194	192	206
Physical state	liquid	liquid	liquid
Vapour pressure Pa (measured)	2.2	2.1	0.67
Water solubility mg/l (measured)	89	186	57
Log Kow (measured)	4.5	3.9	4.4
Log Kow (calculated – ECOSAR)	3.1	2.85	3.34
Acute Aquatic toxicity
LC50 Fish mg/l Exp	15.8 RA from Cyclacet	15.8	6.7
EC50 Daphnia mg/l Exp	25 RA from Cyclacet	25	>14
EC50 Alga mg/l Exp	25 RA from Cyclacet	25	2.5
EC50 Micro-organisms in mg/l	254 RA from Cyclacet	254
Long-term Aquatic toxicity
EC10/NOEC Fish mg/l Experimental	1.9	1.9 RA using A/C of Cyclaprop	0.8
EC10 Daphnia mg/l	1.8 RA using A/C of Cyclaprop	1.8 RA using A/C of Cyclaprop	>=1
EC 10/NOEC Algae mg/lExp	3.2 RA from Cyclacet	3.2	1.9
EC10 Micro-organisms	53 RA from Cyclacet	53

RA is read across; Exp=Experimental;