2-tert-pentylcyclohexyl acetate

Endpoint summary

Description of key information

For Coniferan the following effect values were derived based on read across from Verdox and Cyclaprop.

Guideline	Test species	Endpoint	Result	Remark
OECD TG 203	Danio rerio	96 -h LC50	5.3 mg/L	Data derived from read-across to Verdox (CAS# 20298-69-5). Semi-static conditions and measured concentrations were used. Key study; rel. 1
OECD TG 210	Pimephales promelas	33 -d NOEC	0.67 mg/L	Data derived from read-across to Cyclaprop (CAS# 68912-13-0). Flow-through conditions and measured concentrations were used. Key study; rel. 1
EU TM C.2	Daphnia magna	48 -h EC50	16.2 mg/L	Data derived from read-across to Verdox (CAS# 20298-69-5). Static conditions and measured concentrations were used. Key study; rel. 1
OECD TG 211	Daphnia magna	21 -d NOEC	0.84 mg/L	Data derived from read-across to Cyclaprop (CAS# 68912-13-0). Flow-through conditions and measured concentrations were used. Key study; rel. 2
OECD TG 201	Desmodesmus subspicatus	72 -h ErC50	4.0 mg/L	Data derived from read-across to Verdox (CAS# 20298-69-5). Static conditions and measured concentrations were used. Key study; rel. 1
OECD TG 201	Desmodesmus subspicatus	72 -h NOErC	0.54 mg/L	Data derived from read-across to Verdox (CAS# 20298-69-5). Static conditions and measured concentrations were used. Key study; rel. 1
OECD TG 301F	Activated sludge	61 -d NOEC	95.2 mg/L	Data derived from read-across to Verdox (CAS# 20298-69-5). Static conditions were used. Key study; rel. 1

Additional information

Aquatic toxicity of Coniferan (CAS #67874-72-0) using read across from Verdox (CAS #20298-69-5) and Cyclaprop (CAS #68912-13-0).

Introduction and hypothesis for the analogue approach

Coniferanis an acetate-ester attached to a cyclohexyl ring with a tert-pentyl-group attached at the ortho-position. 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 information of Coniferan the analogue approach is selected because for a closely related analogue, Verdox, aquatic toxicity information is available which can be used for read across. For the long-term aquatic toxicity the results of another analogue, Cyclaprop, will be used for read across.

Hypothesis: Coniferan has similar aquatic toxicity potential as Verdox and as Cyclaprop asboth substances are esters attached to cyclohexyl rings without any additional reactive functional groups. Therefore, the substances’ octanol-water partitioning coefficients (log Kow) are considered to give direct indication of their toxicities.

Available information: No aquatic toxicity data are available for the target chemical Coniferan. For the source chemical Verdox data are available from GLP guideline studies with fish, aquatic invertebrates, algae and micro-organisms. Short-term effect values for Verdox were determined to be in the range of 1-100 mg/L for fish, Daphnia, and algae. NOEC values were available for algae and micro-organisms, being 0.5 and 100 mg/l, respectively. The long-term aquatic toxicity data of Cyclaprop will be used for assessing the long-term effects. Its NOEC fish is 0.8 mg/l, NOEC Daphnia is ≥ 1 mg/l and NOEC algae is just above 1 mg/l. All tests are according to current OECD guidelines.

In more detail: for Verdox a short-term fish study was performed according to OECD 203 and in compliance with GLP criteria (Bayer, 1994). The 96-h LC50 value is 5.6 mg/L in zebrafish (D. rerio). The data are reliable without restrictions (Klimisch 1).An aquatic invertebrates study wasperformed according to OECD TG 202 and in compliance with GLP criteria (Bayer, 1994). The 48-h EC50 is 17 mg/L inDaphnia magna. The data are reliable without restrictions (Klimisch 1).An aquatic algae study was performed according to OECD TG 201 and in compliance with GLP criteria (IFF, 2011). The 72-h ErC50 and ErC10 values are 4.2 mg/L and 0.57 mg/L, respectively in green algae (D. subspicatus). The data are reliable without restrictions (Klimisch 1). For micro-organism a NOEC was derived from a toxicity control in a ready biodegradability test and is 100 mg/l. For Cyclaprop recent long-term fish, Daphnia and algae studies are available according to OECD TG, 210, 211, and 201, respectively, under GLP and all Klimisch 1.

Target chemical and source chemical

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

Coniferan is a multi-constituent containing two stereo isomers. The purity of Coniferan is close to 100%. In view of Verdox also being a multi-constituent containing two stereo isomers and having a purity close to 100%, there will be no significant impurities relevant for read across. Cyclaprop is a reaction mass containing two major components in which the position of the double bond can be at the 5-yl or 6-yl. These constituents will have the same aquatic toxicity.

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. Verdox was selected for read across because it was the most similar substance when compared to other cyclohexyl acetic esters such as presented in Belsito et al., 2008 (ECHA, 2017, RAAF). Cyclaprop is selected because it is a similar ester for which long-term aquatic toxicity information is available. For other similar esters such long-term information is not available (RIFM database).

Structural similarities and differences:Coniferan and Verdox show very close structural resemblance. Both are esters with acommon cyclohexyl acetate backbone.Coniferan has a one additional methyl group attached to the tert-butyl group i.e. it contains a tert-pentyl group (see data matrix for chemical structures).Cyclaprop has two hydrocarbon rings attached at the ortho- and meta-position, instead of alkyl-chain, which is not expected to present difference in the long-term toxicity. The ester group of Cyclaprop is a propyl group instead of an acetic one, which is also not expected to present much difference in long-term aquatic toxicity and will included when using the log Kow for conversion to Coniferan.

Bioavailability:All substances are esters and do not contain any additional reactive functional groups. Therefore, the substances’octanol-water partitioning coefficients (log Kow) are thus considered to give direct indication of their bioavailability and consequentially their aquatic toxicity potential. 

Reactivity: Coniferan, Verdox and Cyclaprop are expected to have the same reactivity because these substances have the acetic or propyl-ester as the functional group and the one methyl group difference will be considered in their respective log Kow values. 

Comparison of experimental data to support the read across:For Coniferan there is no information that can be used for comparison. Verdox and Cyclaprop present very similar acute aquatic toxicity information indicating that hydrocarbon type of esters with similar log Kow values present similar long-term aquatic results. 

Conversion of the short -term values to Coniferan from Verdox: The difference in log Kow between Verdox and Coniferan will be used for conversion of the toxicity values after and adjustment for molecular weight (Caracal meeting for nonanoic acid, Caracal, 2013).

Effect value Coniferan in mg/l = (Effect value of Verdox in mmol/l x (log Kow Verdox/Log Kow Coniferan) x MW of Coniferan).

Uncertainty of the prediction:There is no remaining uncertainty because the aquatic toxicity values of Verdox were corrected to present the expected higher toxicity for Coniferan based on the higher log Kow of the latter substance. The short-term values of Verdox are very much in line with the short-term values of Cyclaprop. Therefore the long-term aquatic toxicity values of Cyclaprop can be used to predict the long-term toxicity for Coniferan (and for Verdox) using the conversion of the effect values in mol/l and log Kow. Using the ECHA guidance (2017, RAAF) criteria the score receives 5 in view of the reasoning above.

Data matrix

The relevant information on physico-chemical properties and aquatic toxicity are presented in the Data Matrix below.

Conclusions for hazard assessment, environmental classification, PBT assessment and PNEC derivation

Hazard assessment:For Coniferan no experimental aquatic toxicity information is available. Read-across is performed to the structural analogues Verdox and Cyclaprop.Verdox shows short-term toxicity values between 1 and 100 mg/L in fish, Daphnia and algae. For Verdox NOEC values are available for algae and micro-organisms and for Cyclaprop EC10/NOEC values are available for all trophic levels. The algae data of Verdox both short-term and long-term values were the lowest and these were corrected for the higher log Kow values of Coniferan. This results in a lowest short-term effect value of 5 mg/l and a lowest long-term effect value of 0.54 mg/l. For micro-organism the derived NOEC for Coniferan is 95.2 mg/l, also based on data from Verdox.

Classification and labelling: These hazard values derived for Coniferan, in combination with the non-ready biodegradability result, results inAquatic Chronic 2 (H411: Toxic to aquatic life with long lasting effects),according to regulation EC/1272/2008 (CLP).

PBT assessment: Solely based onthe available aquatic toxicity values, the substance is not ‘T’. The substance is also not P and not B as presented in the respective analogue approaches for these endpoints.

PNEC: The PNEC freshwater is determined at 0.054 mg/l. This is based on the lowest chronic effect value available from both read-across source chemicals (the NOEC of 0.54 mg/l in algae), and an assessment factor of 10 (reliable chronic data available for 3 trophic levels).

Data matrix for read across to Coniferan from Verdox and Cyclaprop

Common names	Coniferan	Verdox	Cyclaprop
Chemical name	2-tert-pentylcyclohexyl acetate	2-tert-butylcyclohexyl acetate	3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoindenyl propionate
Chemical structures
Target/Source chemical	Target	Source	Source
CAS No.	67874-72-0	20298-69-5	68912-13-0
EC No.	Registration 2018	243-718-1 (registered)	272-805-7 (registered)
Empirical formula	C13H24O2	C12H22O2	C13H18O2
Molecular weight (MW)	212	198	206
Physico-chemical
Physical state	liquid	Liquid at 30°C	Liquid
Melting point, °C	-20	29.8	-20
Boiling point, °C	252	232	263
Vapour pressure, Pa	4.24 (at 24 °C)	9.72 (23 °C)	0.67 (23 °C)
Water solubility, mg/l	7.6 (at 24 °C)	10 (23 °C)	57 (23 °C)
Log Kow	5.4	4.8	4.4
Log Kow (KowWin)	4.9	4.4	4.9
Environmental fate
Biodegradability	Not readily (NRB)	Not readily (NRB)	Not readily (NRB)
Bioaccumulation	(BCFin vitro, trout hepatocytes)	156 (OECD TG 305)	No data
Aquatic toxicity
Acute Fish in mg/l	Read-across from Verdox: 5.3 (= 0.028 mmol/l x 4.8/5.4 (log Kow) x 212 (MW))	Experimental data: 5.6 (0.028 mmol/l x 198 (MW))	Experimental data: 6.7 (0.033 mmol/l x 206 (MW))
Chronic fish in mg/l	Read-across from Cyclaprop: 0.67 (=0.0039 mmol/l x 4.4/5.4 (log Kow) x 212 (MW))	No experimental data	Experimental data: 0.8 (0.0039 mmol/lx 206 (MW))
Acute Daphnia in mg/l	Read-across from Verdox: 16.2 (=0.086 mmol/l x 4.8/5.4 (log Kow) x 212(MW))	Experimental data: 17 (0.086 mmol/lx 198 (MW))	Experimental data: 14 (0.068 mmol/l x 206 (MW))
Chronic Daphnia in mg/l	Read-across from Cyclaprop: 0.84 (=0.0049 mmol/l x 4.4/5.4 (log Kow) x 212(MW))	Test being performed	Experimental data: ≥ 1 (0.0049 mmol/l x 206 (MW))
Acute Algae in mg/l	Read-across from Verdox: 4.0 (=0.021 mmol/l x 4.8/5.4 (log Kow) x 212(MW))	Experimental data: 4.2 (0.021 mmol/lx 198 (MW))	Experimental data: 2.5 (0.012 mmol/l x 206 (MW))
Chronic Algae in mg/l	Read-across from Verdox: 0.54 (=0.0029 mmol/l x 4.8/5.4 (log Kow) x 212(MW))	Experimental data: 0.57 (0.0029 mmol/lx 198 (MW))	Experimental data: 1.9 (0.008 mmol/l x 206 (MW))
Micro-organisms in mg/l	Read-across from Verdox: 95.2(=0.5 mmol/l x 4.8/5.5 log Kow) x 212(MW))	Experimental data: 100 mg/l (0.5 mmol/l (biodeg. test) x 198 (MW))	No experimental data

References

Caracal, 2013, Committee for Risk Assessment, RAC, Opinion proposing, harmonised classification and labelling at EU level of nonanoic acid, EC number: 203-931-2; CAS number: 112-05-0; CLH-O-0000002588-64-03/F

http://echa.europa.eu/documents/10162/7f5f4e90-ae0a-44dc-862c-2cc8337448aa, pg 14.