α-methylcyclohexylmethyl acetate

Endpoint summary

Description of key information

For Veilex 2 the following effect values were derived:

Guideline	Test species	Endpoint	Results	Remarks
OECD TG 202	Daphnia magna	48-h EC50	8.5 mg/L	Data obtained from read-across*. Static test and measured concentrations were used. Key study; rel. 1
OECD TG 201	Pseudokirchneriella subcapitata	72-h ErC50 72-h ErC10	7.7 mg/L 1.6 mg/L	Data obtained from read-across*. Static test and measured concentrations were used. Key study; rel.1

* Results reported here were derived from read across to CP Formate and corrected for differences in log Kow (i.e. bioavailability) and molecular weight.

Additional information

Below the read across approach is documented. The documents are attached at the respective records.

Aquatic toxicity of Veilex#2 (CAS #13487-27-9) based on read across from data available for CP Formate (CAS #25225-08-5).

Introduction and hypothesis for the analogue approach

Veilex#2 is a cyclohexane-ethyl ester for which no experimental aquatic toxicity data are available. For assessment of the aquatic toxicity potential of Veilex#2 read-across is performed to the close structural analogue CP Formate. In accordance with Article 13 of REACH, lacking information may be generated by other means, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the aquatic toxicity of Veilex#2 the analogue approach is selected because for a closely related analogue, CP Formateaquatic toxicityinformation is available which can be used for read across.

Hypothesis: Veilex #2 has similar aquatic toxicity potential as CP Formate asboth substances are esters without any additional reactive functional groups.

Available information: No aquatic toxicity data are available for the target chemical Veilex #2.For CP Formate experimental data are available. An aquatic algae study was performed according to OECD TG 201. The 72-h ErC50 and ErC10 values are >7.1 mg/L and 1.5 mg/L, respectively. The 48-h Daphnia EC50 is 7.7 mg/L (OECD TG 202). The data are reliable without restrictions (Klimisch 1).

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

Veilex#2 is a mono-constituent with a purity close to 100%. CP Formate is a multi-constituent composed of 65-85% 1-(3,3-dimethylcyclohexyl) ethyl formate and 8-18% 2,6,6-trimethylcycloheptyl formate. The minor constituent has a similar functional group but a larger ring structure of 7- C atoms which will not affect the read across.

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. In accordance with ECHA guidance (2015, RAAF) the analogue CP Formate is selected from a group of esters because CP Formate is structurally the most similar and is considered to present conservative aquatic toxicity when using read across to Veilex #2.

Structural similarities and differences: Veilex#2 (target) and CP Formate (source) are both esters with a common cyclohexane ethyl backbone. In Veilex#2 the ester contains an acetic- group while in CP Formate this is a formic-ester group. The formic group may be more toxic compared to the acetic group because of the formation of formic acid, which is a more reactive group. In addition, CP Formate contains two methyl groups at the cylcohexane ring meta-position which are absent in Veilex#2. These two methyl groups will cause somewhat higher molecular weight and log Kow compared to Veilex#2.

Bioavailability: CP Formate and Veilex#2 have similar bioavailability based on the similarity in chemical structure and physico-chemical properties. The molecular weight of the Veilex#2 and CP Formate are 170 and 184, respectively. They are both liquids. They have similar vapour pressures: Veilex#2 has a slightly higher value as can be expected on the lower molecular weight. For the same reason the water solubility of Veilex#2 is slightly higher and the log Kow slightly lower. These differences are not expected to affect bioavailability. If anything CP Formate may be more bioavailable.

Reactivity: Formates are considered more reactive toxic than acetates based on the potential formation of formic acid when metabolized (e.g. formic acid is more acidic than acetic acid, pKa’s are 3.75 and 4.75, respectively. Therefore CP Formate is considered the more toxic substance. This indicates the CP Formate data can be used for read across to Veilex#2 and being conservative.

Uncertainty of the prediction: There are no remaining uncertainty, CP formate will present a higher toxicity (lower EC50 values) because it is slightly more bioavailable and slightly more reactive. To be consistent a conversion is done based on MW and log Kow resulting in EC50 Daphnia of 8.5 and ErC50 Algae of 7.7 and an EC10 for algae of 1.6 mg/l. Using the RAAF criteria, a value of 5 can be presented (ECHA guidance, 2015, RAAF). Acute Daphnia and algae information on other fragrance type esters are presented (all substances are REACH registered). All substances have EC50’s > 1 mg/l. When log Kow is < 4.4, the NOEC/EC10 values are > 1 mg/l. Veilex#2 has a log Kow of 3.2 and therefore the NOEC for algae can be assumed to be > 1 mg/l.

Table 1: Experimental acute EC50 Daphnia and Algae as well as NOEC/EC10 values for algae on a number of REACH registered fragrance type of esters of which Veilex#2 is one

Substance	EC number	CAS No.	log Kow measured	Acute daphnia measured (mg/l)	Acute alga measured (mg/l)	Chronic alga measured (mg/l)
CP Formate (formic acid)	939-618-9	25225-08-5	3.8	7.7	>7.1	1.5
Cyclacet (acetic acid)	911-369-0	54830-99-8	3.9	25	25	3.2
Cyclaprop (propionic acid)	272-805-7	68912-13-0	4.4	>14	2.5	1.95
Cyclobutanate (butanoic acid)	441-420-8	113889-23-9	4.48	4.7	1.95	1.163
Terpinyl acetate (acetic acid)	201-265-7	80-26-2	4.5	10	6.9	1.3
Verdox (acetic acid)	243-718-1	20298-69-5	4.8	17	17	1.3

* CAS numbers are sometimes assigned to a generic substance and may not have been registered as such.

Conclusions for hazard assessment and environmental classification

Hazard assessment: For Veilex #2 no aquatic toxicity information is available but data are available for a close analogue CP Formate. After conversion these values result in EC50 for Daphnia is: 8.5 mg/l and the ErC50 and EC10 for algae are: 7.7 and 1.6 mg/l, respectively.

Classification and labelling: The EC50’s being between 1 and 10 mg/l, the NOEC algae > 1 mg/, the substance being readily biodegradable and the log Kow < 4, classification is not needed according to CLP.

Data matrix presenting the information to read across for Veilex #2 from CP Formate

Common name	Veilex#2	CP Formate
Chemical name	α-methylcyclohexylmethyl acetate	α,3,3-trimethylcyclohexylmethyl formate
Chemical structures	see read across justification document	see read across justification document
CAS No.	13487-27-9	25225-08-5
EINECS	236-798-4	246-735-2
Empirical formula	C10H18O2	C11H20O2
Molecular weight	170	184
Physical state	liquid	liquid
Melting point, °C	<-20	-20
Boiling point, °C	215.7	219.9
Vapour pressure, Pa	38.5 (at 24°C)	13.4 (at 23°C)
Water solubility, mg/l	43.0 (at 24°C)	26.1 (at 23°C)
log Kow	3.2	3.8
Aquatic toxicity
Aquatic invertebrates EC50 in mg/L	Read across from CP Formate: 8.5 (=0.042 mmol/l x 3.8/3.2 (log Kow) x 170 (mw))	Used for read across: 7.7 mg/L (0.042 mmol/l x 184.3 (mw))
Aquatic algae 72-h ErC50 in mg/l 72-h ErC10 in mg/l	Read across from CP Formate: 7.7 (=0.038 mmol/l x 3.8/3.2 (log Kow) x 170 (mw)) 1.6 (=0.008 mmol/l x 3.8/3.2 (log Kow) x 170 (mw))	Used for read across: 7.1 mg/L (0.038 mmol/l x 184 (mw)) 1.5 mg/L (0.008 mmol/l x 184 (mw))