Reaction mass of 3a,4,5,6,7,7a-hexahydro-4,7-methanoinden-5-yl acetate and 3a,4,5,6,7,7a-hexahydro-4,7-methanoinden-6-yl acetate

Endpoint summary

Description of key information

The aquatic toxicity studies for Cyclacet are listed in the table below:

Method	Test species	Endpoint	Result	Remarks
OECD TG 203	Brachydanio rerio	96h-LC50	15.8 mg/l	Key study, GLP, rel. 1
Read across and conversion	Pimephales promelas	33 -d NOEC 33 -d EC10	1.9 mg/l 2.1 mg/l	Key study, GLP, rel. 2 Read across from Cyclaprop, which was tested in an OECD TG 210
OECD TG 202	Daphnia magna	48h-EC50	25 mg/l (nominal because > 80% measured)	Key study, GLP, rel. 1
Read across and conversion	Daphnia magna	21d-NOEC	1.8 mg/l (nominal, because > 80% measured)	Key study, GLP, rel. 2 Read-across from Cyclaprop, which is tested in an OECD TG 211)
OECD 201	Desmodesmus subspicatus	72h-ErC50 72h-ErC10	6.4 mg/l (geometric mean)  2.0 mg/l (geometric mean)	Key study, GLP, rel. 1
OECD TG 209	Activated sludge	EC50 EC10	245 mg/l 53 mg/l	Key study, GLP, rel. 2

Additional information

The long-term toxicity of Cyclacet for fish and Daphnia is derived from Cyclaprop. The read across is documented below.

Cyclacet’s (EC no:911-369-0) long-term fish and Daphniatoxicity using read across and conversion from Cyclaprop (EC no.272-805-7)

Introduction and hypothesis for the analogue approach

Cyclacet has a tricyclodecenyl fused ring structure backbone to which an acetic ester is attached. For this substance, no long-term aquatic toxicity data on vertebrates and invertebrates are available. In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such as QSARs, grouping and read-across. For assessing the chronic aquatic toxicity of Cyclacet the analogue approach is selected because for Cyclaprop, a closely related analogue reliable chronic data are available.

Hypothesis: Cyclacet has similar chronic fish and Daphnia toxicity compared to Cyclaprop after conversion.

Available experimental information:Cyclacet and Cyclaprop have a full base set for aquatic toxicity (algae acute and chronic EC10/NOEC, Daphnia, fish and micro-organisms) all receiving Klimisch 1. For Cyclaprop, EC10/NOECs are available also for fish and Daphnia. All values are derived with OECD Testing guideline methods and according to GLP.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix.

Purity / Impurities

Cyclacet is a reaction mass, containing two very similar isomers in which the double bond is at the 5-yl or 6 yl position. Impurities are all below 1%. 

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.

Structural similarities and differences:Cyclacet (target) and Cyclaprop (source) both have a tricyclodecenyl fused ring structure with an unsaturated bond in the outside ring. On the other side of the ring an ester bond is attached with a short alkyl chain. The alkyl chain of Cyclacet is an ethyl chain while the Cyclaprop has a propyl one and this shorter chain results in a slightly lower log Kow of Cyclacet compared to Cyclaprop.

Bioavailability:Cyclacethas similar bioavailability based on the similarity in chemical structure and physico-chemical properties compared to Cyclaprop as presented in the Data matrix.

Mode of Action(MoA): Cyclacet has the same mode of action as Cyclaprop based on their similar backbone and their similar functional ester group (see Data matrix). This same MoA of action has resulted in an incremental increase of acute LC50 and EC50 values for fish, algae, and Daphnia based on the decreased alkyl chain: Cyclacet is slightly less toxic compared to Cyclaprop.

Chronic aquatic toxicity: There are two methods to determine the chronic toxicity towards aquatic organisms. Firstly, Cyclacet’s long-term fish and Daphnia toxicity can be predicted by applying the A/C ratio of Cyclaprop using the acute toxicity data of Cyclacet. This reflects the long-term toxicity best because the experimental acute data from Cyclacet are included and therefore more certain. 

Secondly, Cyclacet’s long-term toxicity for fish and Daphnia can be predicted from Cyclaprop using converting the Cyclaprop values using molecular weight and log Kow differences. This method will be used for support (see for calculations Table 1), the used formula is: Log NOEC/EC10 target (mmol) = Log NOEC/EC10 source (mmol) x log Kow source/Log Kow target.

Fish: Cyclacet is predicted to have an EC10 of 2.1 mg/l (15.8 mg/l/ 7.4, the latter values is A/C ratio of the acute / long-term fish toxicity of Cyclacprop (see Data matrix)).

Daphnia: Cyclacet is predicted to have an EC10 of 1.8 mg/l (25 mg/l / 14 (the latter value is the A/C ratio of Cyclaprop (see Table 1).

Uncertainty of the predictions:The prediction by read across using the A/C ratio is supported with predictions using conversion based on molecular weight and log Kow as is presented in the Data matrix. There are no other uncertainties than already addressed above.

Data matrix

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

Conclusions for long-term fish and Daphnia toxicity

Cyclacet’s (EC no:911-369-0) long-term fish and Daphniatoxicity using read across and conversion from Cyclaprop (EC no.272-805-7)

Introduction and hypothesis for the analogue approach

Cyclacet has a tricyclodecenyl fused ring structure backbone to which an acetic ester is attached. For this substance, no long-term aquatic toxicity data on vertebrates and invertebrates are available. In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such as QSARs, grouping and read-across. For assessing the chronic aquatic toxicity of Cyclacet the analogue approach is selected because for Cyclaprop, a closely related analogue reliable chronic data are available.

Hypothesis: Cyclacet has similar chronic fish and Daphnia toxicity compared to Cyclaprop after conversion.

Available experimental information:Cyclacet and Cyclaprop have a full base set for aquatic toxicity (algae acute and chronic EC10/NOEC, Daphnia, fish and micro-organisms) all receiving Klimisch 1. For Cyclaprop, EC10/NOECs are available also for fish and Daphnia. All values are derived with OECD Testing guideline methods and according to GLP.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix.

Purity / Impurities

Cyclacet is a reaction mass, containing two very similar isomers in which the double bond is at the 5-yl or 6 yl position. Impurities are all below 1%. 

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.

Structural similarities and differences:Cyclacet (target) and Cyclaprop (source) both have a tricyclodecenyl fused ring structure with an unsaturated bond in the outside ring. On the other side of the ring an ester bond is attached with a short alkyl chain. The alkyl chain of Cyclacet is an ethyl chain while the Cyclaprop has a propyl one and this shorter chain results in a slightly lower log Kow of Cyclacet compared to Cyclaprop.

Bioavailability:Cyclacethas similar bioavailability based on the similarity in chemical structure and physico-chemical properties compared to Cyclaprop as presented in the Data matrix.

Mode of Action(MoA): Cyclacet has the same mode of action as Cyclaprop based on their similar backbone and their similar functional ester group (see Data matrix). This same MoA of action has resulted in an incremental increase of acute LC50 and EC50 values for fish, algae, and Daphnia based on the decreased alkyl chain: Cyclacet is slightly less toxic compared to Cyclaprop.

Chronic aquatic toxicity: There are two methods to determine the chronic toxicity towards aquatic organisms. Firstly, Cyclacet’s long-term fish and Daphnia toxicity can be predicted by applying the A/C ratio of Cyclaprop using the acute toxicity data of Cyclacet. This reflects the long-term toxicity best because the experimental acute data from Cyclacet are included and therefore more certain. 

Secondly, Cyclacet’s long-term toxicity for fish and Daphnia can be predicted from Cyclaprop using converting the Cyclaprop values using molecular weight and log Kow differences. This method will be used for support (see for calculations Table 1), the used formula is: Log NOEC/EC10 target (mmol) = Log NOEC/EC10 source (mmol) x log Kow source/Log Kow target.

Fish: Cyclacet is predicted to have an EC10 of 2.1 mg/l (15.8 mg/l/ 7.4, the latter values is A/C ratio of the acute / long-term fish toxicity of Cyclacprop (see Data matrix)).

Daphnia: Cyclacet is predicted to have an EC10 of 1.8 mg/l (25 mg/l / 14 (the latter value is the A/C ratio of Cyclaprop (see Table 1).

Uncertainty of the predictions:The prediction by read across using the A/C ratio is supported with predictions using conversion based on molecular weight and log Kow as is presented in Table 1. There are no other uncertainties than already addressed above.

Data matrix

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

Conclusions for long-term fish and Daphnia toxicity

For Cyclacet only acute toxicity information for fish and Daphnia is available. However, there are no experimental long-term fish and Daphnia available. For Cyclaprop chronic data are available, which can be used for read across. In case of using read across the result derived should be applicable for risk assessment and be presented with adequate and reliable documentation. This documentation is presented in the current document. For Cyclaprop the LC and EC50 of fish and Daphnia are 6.7 and > 14 mg/l, while EC10/NOECs are 0.91 and 1 mg/l, respectively, resulting in acute / chronic (A/C) ratios of 7.4 and 14. These A/C ratios can be applied to the acute LC50 and EC50 values of Cyclacet, which are 15.8 and 25 mg/l, respectively.

Final conclusion on hazard: Cyclacet has EC10/NOECs for fish and Daphnia of 2.1 and 1.8 mg/l.

 

Data matrix to assess the long-term toxicity of fish and Daphnia of Cyclacet using the acute/chronic (A/C) ratio found for Cyclaprop read across from Cyclaprop

Common names	Cyclacet	Cyclaprop
	Target	Source
Chemical structures
Cas no of the main isomer Cas no of the generic	2500-83-6 (5-yl) 54830-99-8	- 68912-13-0
Empirical formula	C12H16O2	C13H18O2
EC number	911-369-0	272-805-7
REACH registration	Registered	Registered
Molecular weight	192	206
Physico-chemical data
Physical state	liquid	liquid
Boiling point °C	247	263
Vapour pressure Pa	2.1	0.67
Water solubility mg/l	186	57
Log Kow	3.9	4.4
Acute Aquatic toxicity
LC50 Fish mg/l E	15.8 (OECD TG 203)	6.7 (OECD TG 203)
EC50 Daphnia mg/l	25 (OECD TG 202)	>14 (OECD TG 202)
EC50 Algae mg/l	6.4 (OECD TG 201)	2.5 (OECD TG 201)
Long-term Aquatic toxicity
Fish EC10/NOEC mg/l	2.1 (RA using A/C ratio of Cyclaprop) 1.7 (RA using conversion MW and log Kow from Cyclaprop)	0.91 (OECD TG 210) (A/C = 7.4)
Daphnia EC10/NOEC mg/l	1.8 (RA using A/C ratio of Cyclaprop) 1.4 (RA using conversion MW and log Kow from Cyclaprop)	≥1 OECD TG 211 A/C = 14)
Algae mg/l EC10 /NOEC mg/l	2 (OECD TG 201)	1.9 (OECD TG 201)

RA is read across;

 

Table 1 Conversion to Cyclacet from Cyclaprop

Substance	Species	EC10 in mg/ Cyclaprop	MW Source	Mmol/L Source	Log mMol/l Source	Log Kow source	Log Kow target	Convert to Log Mmol/l target	Convert to 10^	MW Target	EC 10/NOEC in mg/l Cyclacet
Cyclacet	Algae	3,2	206	0.0155	-1.8087	4,4	3,9	-1.60318	0.0249	192	4.787624
	Daphnia	1	206	0.0048	-2.3138	4,4	3,9	-2.,05093	0.0089	192	1.7075501
	Fish	0,8	206	0.00388	-2.4107	4,4	3,9	-2.,13683	0.0073	192	1.401122