Decahydrospiro[furan-2(3H),5'-[4,7]methano[5H]indene]

Endpoint summary

Description of key information

In the table below the acute aquatic toxicity data are summarised

Species	Method	Result in mg/L	Remarks
Pseudokirchneriella subcapitata	Read Across	EC50 growth rate > 1.59 mg/L EC10 growth rate = 0.62 mg/L  Based on read across information from Cedramber (OECD TG 201)	Key study, Rel 2,
Daphnia magna	Read Across	EC50 48h = 0.42 mg/L Based on read across information from Cedramber (OECD TG 202)	Key study, Rel 2,

Additional information

Vigoflor and its Aquatic Toxicity for Algae and Daphnia using read across information from Cedramber

 

Introduction and hypothesis for the analogue approach

Vigoflor has a hydrocarbon backbone with a cyclic ether; it contains a bridged cyclohexane attached to two 5-ring structures: a cyclopentane and in the other 5-ring (oxacyclopentane) an ether group is incorporated. For this substance no experimental aquatic toxicity data are 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 aquatic toxicity of Vigoflor the analogue approach is selected because for one closely related analogue reliable algae and Daphnia data are available.

Hypothesis: Vigoflor has a similar aquatic toxicity (EC50 and EC10) compared to Cedramber when the results are converted using log Kow and molecular weight. This read across is based on a similar hydrocarbon backbone and ether as a functional group, resulting in a Neutral organic mode of action for both substances.

Available experimental information: No experimental aquatic toxicity data are available for Vigoflor. For Cedramber, however, reliable experimental aquatic toxicity data are available for algae and Daphnia. An Algae Growth Inhibition test, according to OECD 201, and a Daphnia sp. Acute Immobilization Test, according to OECD 202, are available, both receiving Klimisch 1.

More in detail: For Cedramber astudy was performed to assess the acute toxicity of the substance to Daphnia magna under semi-static conditions. The study was conducted in accordance with OECD Guideline for Testing of Chemicals No. 202. Groups of twenty Daphnids were exposed for 48 hours to six concentrations of the substance dispersed in test water (1.0 - 46 % of a WSF prepared at a loading rate of 100 mg/L) and a control. The incidence of immobilisation was recorded for each test and control group at 24 hours and at 48 hours and the following endpoint was determined: 48-h EC50 = 0.48 mg/L. All results are expressed in terms of geometric mean measured concentrations.

In addition a study was performed for Cedramber to assess the effect of the test material on the growth of the green alga Pseudokirchneriella subcapitata, strain: N1.The method followed that described in the OECD TG No 201. Pseudokirchneriella subcapitata was exposed to a Water Soluble Fraction (WSF) prepared at a loading rate of 100 mg/L and 5 dilutions of this WSF and a control for 72 hours. Measured concentrations decreased steadily throughout the course of the test: the lowest two concentrations were not detectable anymore at t = 72h. Therefore TWA measured concentrations were calculated and used for expression of endpoints. Statistically significant inhibition of growth rate was found at and above the TWA measured concentration of 0.51 mg/L. The ErC10 and ErC50 based on TWA measured concentrations were 0.70 and >1.8 mg/L, respectively. The NOErC was set at 0.51 mg/L.

Target chemical and source chemical(s)

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

Purity / Impurities

Vigoflor has two constituents that are stereo-isomers of each other, which indicate the same aquatic toxicity 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.

Analogue selection:Clear documentation is needed on the selection of potential source substances. In the RIFM Database no analogues were identified for Vigoflor. A further search in the OECD QSAR toolboxby using structural similarity with Tanimoto 60% on Atom Pairs, Atom Centred Fragments or a combined search on both molecular features revealed no analogues. Cedramber is selected from IFFs portfolio: it has a similar functional group, ether, and has a similar hydrocarbon backbone. Also Amber Xtreme (EC no 449-360-4), was selected from IFFs portfolio and considered for the analogue approach but the acute aquatic toxicity values for algae and Daphnia for this substance were above the water solubility and therefore deriving the values for Vigoflor was not possible. Cedramber was therefore selected as the appropriate analogue for the aquatic endpoints.

Structural similarities and differences:Vigoflor and Cedramber both contain hydrocarbon cyclic rings and an ether group. Vigoflor contains a bridged cyclohexane with attached two 5-ring structures: a cyclopentane and an oxacyclopentane. Cedramber contains a bridged cycloheptane with attached a cyclopentane. In Vigoflor the ether group is incorporated in one of the 5-rings whereas in Cedramber the ether group is not incorporated in, but attached to the cycloheptane. In addition Cedramber contains three methyl groups attached to the cycloheptane and one methyl group to the cyclopentane. This results in a higher molecular weight for Cedramber because of additional hydrocarbon groups without other structural important features.

Bioavailability:Vigoflor and Cedramber have similar bioavailability based on the similarity in chemical structure and physico-chemical properties. The molecular weight of Vigoflor is 192.29, whereas for Cedramber it is 236.39. They are both liquids. They have similar Log Kow’s 4.7 and 5.1 respectively, and water solubility’s of 4.64 and 4.3 mg/L, respectively. It can be seen that the vapour pressure of Vigoflor, is somewhat higher to Cedramber (1.97 Pa, and 0.5 Pa, respectively), which can be expected based on the lower molecular weight of Vigoflor.

Mode of Action and the prediction of the aquatic toxicity information:Vigoflor and Cedramber are expected to have the same Neutral organic mode of action based on their similarity in backbone and the ether functional group. The neutral organic mode of action is supported by ECOSAR and the OECD Toolbox using the Verhaar rules. In view of Vigoflor and Cedramber presenting similar physico-chemical properties and a similar mode of action aquatic toxicity data for algae and Daphnia from Cedramber can be used for read across to Vigoflor.

Conversion:In view of the slight difference in log Kow and molecular weight between Vigoflor and Cedramber the aquatic toxicity data are corrected:

For the aquatic Daphnia toxicity the 48-h EC50 = 0.48 mg/L for Cedramber is converted resulting in a 48-h EC50 = 0.42 mg/L for Vigoflor using following equation: 

0.48 mg/L Cedramber/ 236.39 MW Cedramber * (log Kow 5.1/4.7 IFF measured values Cedramber/Vigoflor) * 192.29 MW Vigoflor = 0.42 mg/L for Vigoflor

A similar conversion is used to calculate the aquatic algae toxicity for Vigoflor resulting in ErC50 >1.59 and ErC10 = 0.62 mg/L

Uncertainty of the prediction: The measured water solubility of Vigoflor, using the shake flask method, is somewhat low (0.22 mg/L). Based on the measured log Kow (4.7) the calculated water solubility (EpiSuite) was considered to be the more reliable value (4.6 mg/L). This calculated water solubility value result in acute aquatic toxicities below the water solubility and is thus a conservative approach.

The aquatic toxicity data are in line with the ECOSAR Neutral organic type of predictions when using the measured log Kow and the aquatic toxicity is in line with the correctly predicted and measured values of Cedramber. In view of the above there is no remaining uncertainty.

Data matrix

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

Conclusions per endpoint for Hazard and C&L

When using read across the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

For Cedramber the following values are derived: for Daphnia 48-h EC50 = 0.48 mg/L and for algae the ErC50 > 1.8 mg/L and the ErC10 = 0.70 mg/L. In view of the similarity in structure and Neutral organic mode of action for Vigoflor converted values can be used resulting in Daphnia 48-h EC50 = 0.42 mg/L and for algae ErC50 >1.59 and ErC10 = 0.62 mg/L.

Final conclusion on hazard and C&L:

For Vigoflor for Daphnia 48-h EC50 = 0.42 mg/L and for algae ErC50 >1.59 and ErC10 = 0.62 mg/L values are derived. In addition, the substance is not readily biodegradable with a log Kow of 4.7. Based on these results Vigoflor needs to be classified for acute aquatic hazard, Category Acute 1, H400: Very toxic to aquatic life and for long-term aquatic hazard, Category Chronic 1, H410: Very toxic to aquatic life with long lasting effects, according to Regulation 1272/2008/EC (CLP) and its amendments.

Data matrix for assessing the aquatic toxicity of Vigoflor using Cedramber for read across.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              

Common names	Vigoflor	Cedramber
Chemical structures
Cas no	68480-11-5	67874-81-1 19870-74-7
EC number	270-887-9	267-510-5
Reach registration	Registered for 2018	Registered for 2018
Physico-chemical data
Molecular weight	192.29	236.39
Physical state	Liquid	Liquid
Melting point °C	<-20	<-20
Boiling point °C	262.8	280.8
Vapour pressure Pa	1.97	0.5
Water solubility mg/L	4.64	4.3
Log Kow (measured)	4.7	5.1
Log Kow (calculated - EPISUITE)	3.59	5.0
Log Kow (calculated - SPARC)	3.78	5.5
Acute Aquatic toxicity
Daphnia (48-h EC50) mg/L	0.42 Read across from Cedramber	0.48 (OECD TG 202)
Algae (72-h ErC50) mg/L	>1.59 Read across from Cedramber	>1.8 (OECD TG 201)
Long-term Aquatic toxicity
Algae (72-h ErC10) mg/L	0.62 Read Across from Cedramber	0.70 (OECD TG 201)