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

Endpoint summary

Description of key information

The substance is a sensitiser, based on read-across from Geranyl Acetate tested in OECD TG 429.

Respiratory sensitisation: not respiratory sensitising, in absence of human data and absence of respiratory sensitisation alerts.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitisation is assessed based on read-across from Geranyl acetate to Neryl acetate multi. The executive summary of the source information is presented below followed by the read-across rationale.

Skin sensitisation:

A local lymph node assay was performed according to OECD TG 429 with Geranyl acetate (trade name Geranylacetat EXTRA; pure E-isomer). Mean disintegrations per minute (dpm)/animal (2 lymph nodes) were 380.9, 1885.1, 2791.1 and 2879.3 for control group and groups exposed to 25, 50, or 100% test substance, respectively. This correlates to SI values of 4.95, 7.33 and 7.56 for the groups dosed at 25, 50 and 100%, presenting skin sensitisation. Based on the calculation method described in NIH Publication Number 11-7709, an EC3 of 13.74 can be derived, resulting in skin sensitiser Cat 1B. The calculation is presented in the read across document.

The skin sensitizing properties of Neryl acetate multi using read across from Geranyl acetate (EXTRA, pure; CAS# 105-87-3)

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 is no experimental information on skin sensitizing properties are available. In accordance with Article 13 of REACH, lacking information can be generated by other means than experimental testing, i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin sensitizing properties of Neryl Acetate multi the analogue approach is selected because for one of the constituents, Geranyl acetate (EXTRA, pure E-isomer), information on skin sensitizing properties is available which can be used for read across.

Hypothesis: Neryl acetate multi has the same skin sensitisation potential as Geranyl acetate.

Available information: For Geranyl acetate a Local Lymph Node assay was performed according to OECD TG 429). SI values of 4.95, 7.33 and 7.56 for the groups dosed at 25, 50 and 100% were recorded. These data indicate that the substance has skin sensitising properties. Based on the calculation method presented in the publication: NIH Publication Number 11-7709 (2011), an EC3 of 13.74 can be derived (see equation for calculation behind the data matrix).

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemicals are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for skin sensitization, of all substances.

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 minor constituent Geranyl acetate is selected as an analogue because it is the closest analogue and for this substance in vivo LLNA information is available.

Structural similarities and differences: Neryl acetate multi has two constituents which are the Z and E-Isomer respectively, which are the same only differing in Z and E isomerisation, which will not result in difference in electrophilicity because there is no hindrance of other groups.

Skin absorption: Neryl acetate multi constituents, Z and E-Isomer have the same kinetic properties, because these are the same only differing in isomerisation. 

Skin sensitisation reactivity: Neryl acetate multi constituents, Z and E-Isomer have the same reactivity because the isomerisation does not influence the electrophilicity because the electrophilic site is the unsaturated bond conjugated with the acetate, which are both sufficiently open to be by proteins.

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

Data matrix

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

Conclusions on skin sensitisation

For Neryl acetate multi no experimental skin sensitisation is available but for its minor constituent Geranyl acetate (EXTRA, the E-isomer, pure), information is available and can be used for read across to fill this gap and adequately and reliably documented. For this Geranyl acetate, reliable data are available from a LLNA showing SI values of 4.95, 7.33 and 7.56 for the groups dosed at 25, 50 and 100%, showing skin sensitizing properties with a calculated EC3 of 13.74. This information can be directly used for read across to Neryl acetate multi.

Final conclusion: Neryl acetate multi has an EC3 of 13.74% and is therefore a skin sensitiser 1B.

References:

ICCVAM Test Method Evaluation Report: Usefulness and Limitations of the Murine Local Lymph Node Assat for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans, NIH Publication Number 11-7709, Annex IV (2011);https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-pot/tmer.pdf

 

Data matrix supporting the read across to Neryl acetate multi fromGeranyl acetate for skin sensitisation.

Common name	Neryl Acetate Multi	Neryl Acetate mono	Geranyl Acetate
	Target	Target	Source
Chemical name	Multi-constituent	(2Z)-3,7-dimethylocta-2,6-dien-1-yl acetate	(2E)-3,7-dimethylocta-2,6-dien-1-yl acetate
Chemical structure	Not applicable
% in product	>80%	55-65	35-45
CAS#	16409-44-2	141-12-8	105-87-3
EC#	240-458-0	205-459-2	203-341-5
Empirical formula	C12H20O2	C12H20O2	C12H20O2
MW	Not applicable	196	196
Phys-chem *
Appearance	Liquid	Liquid	Liquid
Ws (mg/L)	28.8 (exp.)	18.2 (est.)	18.2 (est.)
log Kow	4.6 (exp.)	4.5 (est.)	4.5 (est.)
Human health
Skin sensitisation	EC3 is 13.74% Skin sensitizing Cat. 1B (Read across)	EC3 is 13.74% Skin sensitizing Cat 1B (Read across)	EC3 is 13.74% Skin sensitizing Cat. 1B (OECD TG 429)

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

RA = read-across.

 

Calculation EC3 according to NIH Publication Number 11-7709 (2011), Annex IV (equation in the attached document)

Data used for the calculation:

Concentration	SI value
25%	4.95
50%	7.33
100%	7.26

As all SI values are >3, the following calculation is used:

Where

a = dose concentration for next to lowest SI above 3 (here: 50)

b = next to lowest SI above 3 (here: 7.33)

c = dose concentration for lowest SI above 3 (here: 25)

d = lowest SI above 3 (here: 4.95)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The substance is not a respiratory sensitiser in absence of human data indicating such effects. In addition, the respiratory sensitisation is assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-2, 2014).

1) The substance is a skin sensitiser;

2) The substance does not belong to the di-isocyanates;

3) The substance has no structural alerts or is structurally related to chemicals causing respiratory sensitisation as presented in Table R.7.3-1 in the ECHA guidance of 2008 or those provided in the following document: http://ec.europa.eu/health/scientific_committees/docs/annex6_respiratory.pdf

Therefore the substance is not considered to be a respiratory sensitiser.

Justification for classification or non-classification

Based on the results from an in vivo skin sensitisation study, the substance is considered a skin sensitiser and needs to be classified for Skin sensitisation Category 1B and shall be labelled with 'H317: May cause an allergic skin reaction', according to EU CLP (EC No. 1272/2008 and its amendments).

In absence of human data indicating respiratory sensitisation and using the ITS in the ECHA guidance (R.7a, 2014) the substance is not considered to be a respiratory sensitiser in accordance with the criteria outlined in the EU CLP (EC 1272/2008 and its amendments).