3,7-dimethylocta-2,6-dienyl acetate

Endpoint summary

Description of key information

Skin corrosion: read-across from Linalyl Acetate tested in OECD TG 404: not corrosive

Skin irritation: read-across from Linalyl Acetate tested in OECD TG 404: irritating Cat 2

Eye irritation: read-across from Neryl Acetate mono: OECD TG 405: not irritating

Respiratory inhalation (in absence of human data, and in absence of skin corrosion and eye irritation): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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

Irritation to skin and eye is assessed for Neryl acetate multi is based on read-across from Linalyl Acetate and Neryl Acetate mono. The executive summaries of the source information are presented below followed by the read-across rationale.

Skin irritation for Linalyl acetate

For Linalyl acetate anin vivo skin irritation studyis available according to OECD TG 404 (Rel. 1). In this study, 0.5 mL undiluted Linalyl acetate was applied semi-occlusive for 4 hours to intact rabbit skin in 7 rabbits, observations were made 1, 24, 48 and 72 hours and 7 days after removal of the test item. Erythema and Edema scores averages on the first 3 days were 1.9 and 1.2, respectively. Absence, mild and moderate desquamation from skin surface was seen in 1, 3 and 3 animals, respectively, at day 7, the final observed day. Although the observation time was not extended to investigate reversibility, the severity of the skin effects decreased for most rabbits in the first week after exposure. Not based on the scores, during the first 3 days but based on the desquamation findings at day 7 the substance is an irritant but not corrosive to skin.

Eye irritation for Neryl acetate mono

For Neryl acetate mono an in vivo skin irritation study is available according to OECD TG 405 and in compliance with GLP criteria. In this study, 4 female albino rabbits were exposed to 0.1 ml of the test item in the left eye. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours after dosing. Slight signs of irritation were observed on the treated eyes (mean values for redness and oedema of conjunctive of 0.33-0.67). All effects were fully reversible within 72 hours. Based on these data it is concluded that Neryl acetate mono is not corrosive and not irritant to the eye.

Respiratory irritation:

For respiratory irritation mostly human data are used for the assessment because no suitable in vitro or in vivo tests are available that can identify respiratory irritation. There are no human data such as indicated in R7.2.3 of the ECHA guidance that indicate respiratory reactions of the substance e.g. from consumer experience or occupational exposure. In addition, the substance is not corrosive or severely irritating which further minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2).

The skin and eye irritation of Neryl acetate multi using read across from Linalyl acetate (CAS# 115-95-7) and Neryl acetate mono (CAS# 141-12-8).

 

Introduction and hypothesis for the analogue approach

Neryl acetate multi is a multi-constituent of Neryl acetate and Geranyl acetate, which are the Z and E-isomers (cis and trans) of each other. This ester has an unsaturated branched alkyl backbone to which an acetate group is attached. For this substance there are no experimental informationon skin and eye irritation are available. In accordance with Article 13 of REACH, lacking information can be generated by other i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin and eye irritation of Neryl acetate multi, the analogue approach is selected because for close structural analogue Linalyl acetate, information on skin irritation is available, and for one of the constituents, Neryl acetate mono, data on eye irritation is available which can be used for read-across.

Hypothesis: Neryl acetate multi has the same skin irritation as Linalyl acetate and has the same eye irritation information as its main constituent, Neryl acetate mono.

Available information on skin irritation: For Linalyl acetate anin vivo skin irritation studyis available according to OECD TG 404 (Rel. 2). In this study, 0.5 mL undiluted Linalyl acetate was applied semi-occlusive for 4 hours to intact rabbit skin in 7 rabbits, observations were made 1, 24, 48 and 72 hours and 7 days after removal of the test item. Erythema and Edema scores averages on the first 3 days were 1.9 and 1.2, respectively. Absence, mild and moderate desquamation from skin surface was seen in 1, 3 and 3 animals, respectively, at day 7, the final observed day. Although the observation time was not extended to investigate reversibility, the severity of the skin effects decreased for most rabbits in the first week after exposure. Not based on the scores, during the first 3 days but based on the desquamation findings at day 7 the substance is an irritant but not corrosive to skin.

Available information on eye irritation: For Neryl acetate monoan in vivo eye irritation studyis available according to OECD TG 405 (Rel. 1). In this study, 4 female albino rabbits were exposed to 0.1 ml of the test item in the left eye. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours after dosing.Slight signs of irritation were observed on the treated eyes (mean values for redness and oedema of conjunctive of 0.33-0.67). All effects were fully reversible within 72 hours. Based on these data it is concluded that Neryl Acetate mono is not eye irritating.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemicals are shown in the data matrix below, including physico-chemical properties and toxicological information, thought relevant for local effects.

Purity / Impurities

Neryl acetate multi is a multi-constituent. The other component is the E-isomer Geranyl acetate; together these have a purity of > 80%. There is one known impurity, which is << 10% and is similar to Neryl acetate.

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.

Analogue selection: For Neryl acetate multi the substance Linalyl acetate is selected because it has a very similar chemical structure for which experimental skin irritation information is available. Neryl acetate mono can be used because it is the key constituent and has experimental eye irritation available.

Structural similarities and differences: Neryl acetate multi constituents have a very similar unsaturated branched backbone compared to Linalyl acetate. The latter has a methyl group close to the acetate and an end-group double bond instead of in the alkene chain. The overall unsaturation and functional group is the same as is shown in its empirical formula.

Neryl acetate mono is the key constituent of the multi being the Z-isomer. The minor constituent is the E-isomer and therefore only differs in planarity but not in electrophilicity or functional group.

Skin and eye tissue absorption:Neryl acetate multi has the same bioavailability based on similarity in structure and physical chemical properties.

Irritation reactivity: Neryl acetate multi constituents and Linalyl acetate are similarly reactive based on the same or similar backbone and functional groups. The eye irritation study of Linalyl acetate shows, however, more irritation compared to Neryl acetate mono.

Uncertainty of the prediction: There are no uncertainties other than those already addressed above.

Data matrix

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

Conclusions on skin and eye irritation

For Neryl acetate multi no experimental skin and eye irritation information is available. For Linalyl acetate skin irritation study and for one of Neryl acetate multi’s key constituents eye irritation study is available, which can be used to fill this gap and this read across has been adequately and reliably documented. Linalyl acetate is a skin irritant in an OECD TG 404 (Rel. 2). Neryl acetate mono is not an eye irritant in an OECD TG 405 (Rel. 1). Both sources can be used for read across to Neryl acetate multi.

Final conclusion:Neryl acetate multi is irritating to the skin but not to the eye.

 

Data matrix Supporting the read across toNeryl acetate multi from Linalyl acetate and Neryl acetate mono for skin and eye irritation, respectively.

Common name	Neryl acetate multi	Neryl acetate mono	Geranyl acetate	Linalyl acetate
	Target	Source Major constituent	Target Minor constituent	Source
Systematic name	Multi-constituent	(2Z)-3,7-dimethylocta-2,6-dien-1-yl acetate	(2E)-3,7-dimethylocta-2,6-dien-1-yl acetate	3,7-dimethylocta-1,6-dien-3-yl acetate
Chemical structure
% in product	>80%	55-65	35-45	Not applicable
CAS#	16409-44-2	141-12-8	105-87-3	115-95-7
EC#	240-458-0	205-459-2	203-341-5	204-116-4
Empirical formula	C12H20O2	C12H20O2	C12H20O2	C12H20O2
MW	19)	196	196	196
Phys-chem *
Appearance	Liquid	Liquid	Liquid	--
Ws (mg/L)	28.8(exp.)	18.2(est.)	18.2(est.)	17.5(est.)
log Kow	4.6 (exp.)	4.5(est.)	4.5(est.)	4.4(est.)
Human health
Skin irritation	Irritating to skin (Read across)	Not available	Irritant (ECHA dissemination)	Irritating to the skin (OECD 404)
Eye irritation	Not eye irritating (Read across)	Not eye irritating  (OECD 405)	Not an eye irritant (ECHA dissemination)	Eye irritant (ECHA dissemination site)

* Physico-chemical properties are calculated with EpiSuite unless stated otherwise i.e. ‘(exp.)’

Justification for classification or non-classification

The substance needs to be classified as Skin irritant Category 2, and shall be labelled with 'H315: Causes skin irritation', according to EU CLP (EC No. 1272/2008 and its amendments).

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