Reaction mass of (1R)‐1‐[(1S)‐3,3‐dimethylcyclohexyl]ethyl relacetate and (1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate

Endpoint summary

Description of key information

Skin corrosion/ irritation: the substance does not cause skin irritation based on a study equivalent to OECD TG 404;

Eye irritation: the substance is not an eye irritant, based on read across from CP Formate which was tested in OECD TG 438.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin corrosion/irritation

The skin (corrosion and) irritation potential of the substance was determined in vivo in a study equivalent to OECD TG 404. A volume of 0.5 mL of unchanged substance per gauze pad with a total of 4 gauze pads per animal was administered to the clipped back of 6 male adult albino rabbits (New-Zealand White) for 4 hours under semi-occlusive conditions. The patch sites were observed for signs of erythema and oedema, and scored according to the Draize scale at 30 to 60 minutes, 24, 48 and 72 hours after patch removal.

No oedema or erythema was observed at any of the patch sites on all six (6) animals. All patch sites had scores of 0 during the observation period. In conclusion, the substance does not cause skin irritation in the dermal irritation study in rabbits.

Eye irritation

In the absence of an eye irritation study with Rosamusk, read across with CP Formate was used to assess this eye irritation of Rosamusk. First the executive summary of the source is presented and thereafter the read-across justification.

Isolated Chicken Eye (ICE) test with CP Formate

In a study, performed according OECD TG 438 and in compliance with GLP, the substance was evaluated for eye irritation potential in the lsolated Chicken Eye (lCE) test. ln addition, the test included a negative control (saline) and a positive control (BAC 5 %). Chicken eyes were obtained from slaughter animals used for human consumption. The isolated chicken eyes were exposed to a single application of 30 µL of the test sample for 10 seconds followed by a 20 mL saline rinse. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells.

The substance caused very slight swelling of the cornea, slight or slight to moderate corneal opacity, and very slight or slight fluorescein retention. The calculated lrritation lndex was 43 (max possible score is 200). The negative control (saline) caused no corneal effects. The positive control BAC 5% caused moderate corneal swelling, severe opacity and severe fluorescein retention. The calculated lrritation lndex was 145. Based on the results of this in vitro study, the substance is considered not to be an ocular corrosive or severe irritant.

Rosamusk (Cas no. 25225-10-9) and its eye irritation properties using read across from CP Formate (Cas no. 25225-08-5)

Introduction and hypothesis for the analogue approach

Rosamusk is a reaction mass. The main constituent has a cyclohexyl hydrocarbon backbone to which methyl groups and an ethyl acetyl ester are attached. In the minor constituent the external carbons are slightly different arranged and result in a heptyl ring and an acetyl ester instead of an ethyl acetyl ester.In accordance with Article 13 of REACH, lacking information can be generated by means other than experimental testing, i.e. applying alternative methods such as QSARs, grouping and read-across.For assessing the eye irritation of Rosamusk the read across approach is applied. For the structural related analogue CP Formate eye irritation information is available, which can be used for read across.

Hypothesis: Rosamusk is not an eye irritant based on absence of eye irritation effect for CP Formate.

Available information: CP Formate is not an eye irritant in a reliable OECD TG 438 (Kl.1)

Target chemical and source chemical(s)

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

Purity / Impurities

Rosamusk is a reaction mass containing a major and a minor constituent resulting in > 80% purity. Other impurities are < 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 and/or on a communal metabolite. 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.

Analogue justification: For Rosamusk, CP formate is selected as an analogue based on similarities in the structure and presence of eye irritation toxicity information from CP Formate.

Structural similarities and differences: Rosamusk’s two constituents have the same backbone and functional ester group as the two constituents of CP Formate. The difference is that Rosamusk has an acetyl acid as part of the acetic ester and CP Formate has a methyl chain as part of the formic ester.

Eye tissue absorption: Irritation effects will also be due to the possibility of penetrating the eye protection layers. Rosamusk and CP Formate have similar features considering physical appearance, molecular weight similar water solubilities. Rosamusk has one carbon more and therefore may be slightly less absorbing compared to CP Formate.

Eye irritation/reactivity: The functional group of both Rosamusk and CP Formate is the ester group. Rosamusk is considered slightly less reactive when comparing the acetate with the formate. This can be indicated using the pKa of the acids, acetic acid has a pKa of 4.75 while formic acid has a pKa of 3.77, this shows that Rosamusk is less acidic compared the CP Formate.

Uncertainty of the prediction: There are no remaining uncertainties other than those which have already been discussed above.

Data matrix

Relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix in Table 1.

Conclusions per endpoint for C&L

For Rosamusk no reliable information is available for eye irritation but this information is available for CP Formate and this can be used for read across. 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. This documentation is presented in the current document. CP Formate is not an eye irritant in the OECD TG 438, chicken eye study. In view of the similarity in structures and slightly lower reactivity of Rosamusk the same conclusion can be drawn for Rosamusk.

Final conclusion: Rosamusk is not an eye irritant.

 

Data Matrix for Rosamusk presenting absence for eye irritation using information from CP Formate

Common names	Rosamusk (Reaction mass)	CP Formate (Reaction mass)
Target / Source	Target (main and minor)	Source (main and minor)
Chemical structures of main constituent
Constituent concentration	65-79%	65-85%
Chemical structure of minor constituent
Constituent concentration	10-20%	8-18
Cas no of the main isomer	25225-10-9	25225-08-5
EC number of the main isomer	246-737-3	939-618-9 (Reaction mass)
REACH registered	Annex VII	REACH registered
Molecular weight	196	184
Physico-chemical data	IFF measured data	IFF measured data
Physical state	Liquid	Liquid
Vapour pressure Pa (measured)	9.1	13.4
Water solubility mg/l	12.6	26.1
Log Kow	4.9	4
Human health
Skin irritation	Not irritant (OECD TG 405)	Not irritant (OECD TG 439)
Eye irritation	Read across	Not irritant (OECD TG 438)

Other information: From the RIFM database for Rosamusk an in vitro skin and eye irritation information is available according to OECD TG 439 and 437, 2019) which showed no irritation in both tissues.

Justification for classification or non-classification

The substance does not need to be classified for skin and eye irritation according to EU CLP (EC No. 1272/2008 and its amendments).