Reaction mass of citronellyl propionate and geranyl propionate and neryl propionate

Endpoint summary

Description of key information

Skin sensitisation potential is based on read across from Geranyl Acetate which is tested in an LLNA (OECD TG 4429) resulting in being a sensitiser 1B

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitisation of Geranyl Propionate is based on read-across from Geranyl Acetate. The executive summary of the source information is presented below followed by the read-across rationale.

Skin sensitisation of Geranyl Acetate :

A local lymph node assay was performed according to OECD TG 429 and following GLP principles. 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 and 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%. These data indicate that the substance has skin sensitizing properties. Based on the calculation method described in NIH Publication Number 11-7709 (https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-pot/tmer.pdf), an EC3 of 13.74 can be derived on which bases it classified as Skin sensitizing Category 1B.

Geranyl propionate’s (EC no. 906-089-0) sensitising properties are based on read across from Geranyl acetate (Cas no. 105-87-3)

Introduction and hypothesis for the read across

Geranyl propionate has a branched alkene hydrocarbon backbone and an ester as a functional group to which a propionic alkyl chain is attached. For this substance no experimental skin sensitisation data are available. In accordance with Article 13 of REACH, lacking information can be generated by means other than experimental testing such as QSARs, grouping and read-across. The data gap of Geranyl propionate is filled by using read across from the analogue Geranyl acetate.

Hypothesis: Geranyl propionate has the same sensitizing properties as Geranyl acetate due to similarity in structure, kinetics and other local toxicological properties.

Available information: For Geranyl acetate a well conducted LLNA test (OECD TG 429, Kl. 1) is available and an EC3 of 13.7% was found. These data shows that the substance has skin sensitisation properties.

Target and Source chemical(s):

The information on Geranyl propionate (target chemical) and Geranyl acetate (source chemical) supporting the read-across are presented in the Data matrix. Also, relevant physico-chemical properties are listed there.

Purity / Impurities:

Geranyl propionate is a multi-constituent containing three similar isomers: Geranyl propionate (50-65%), Citronellyl propionate (20-35%) and Neryl propionate (7-17%). All other impurities are below 1%.

Analogue 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 Geranyl propionate the analogue Geranyl acetate is selected based on similarity in chemical structure and for the latter substance reliable and adequate skin sensitisation information is available.

Structural similarities and differences: Geranyl propionate and Geranyl acetate have the same backbone and the same functional ester group. The other constituent Neryl propionate is the cis-form of Geranyl propionate. The third constituent is Citronellyl propionate which has the same branching but one double bond less in the backbone. Another difference is the propionate versus the acetate group of the analogue: the latter substance has one methyl group less in the alkyl chain.

Dermal absorption: Geranyl propionate, its constituents and Geranyl acetate are both liquids and have similar molecular weights. Also the physico-chemical properties such as log Kow (5.4 and 4.04, respectively) indicate that these substances will be absorbed by the skin to some extent. The somewhat lower log Kow of Geranyl acetate potentially has a higher dermal absorption and therefore the read across result will be conservative.

Skin sensitisation reactivity: Geranyl propionate and Geranyl acetate have the same reactivity because of the double bond in the tail and the conjugated bond with the ester resulting in the same skin sensitisation potential. The Citronellyl propionate constituent does not have a conjugated double bond with the ester and is therefore less reactive and therefore the reactivity of Geranyl acetate is potentially somewhat higher and therefore the read across presents a conservative outcome. The skin irritation and the non-eye irritation in both target and source further support the similarity in reactivity.

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

Data matrix

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

Conclusions for skin sensitisation

For Geranyl propionate no skin sensitisation information is available but for Geranyl acetate such information is available and this can be used to fill the data gap of Geranyl propionate. 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. For Geranyl acetate reliable data are available from a LLNA test (OECD TG 429), showing an EC3% of 13.7% and thus skin sensitisation. This information can be used for read across to Geranyl propionate as is presented in the current document.

Final conclusion: Geranyl propionate has an EC3 of 13.7% and is therefore is a skin sensitiser.

Data matrix of Geranyl propionate (target) and Geranyl acetate (source) to support the skin sensitising potential of the target

Common names	Geranyl propionate	Geranyl acetate
	Target	Source
Chemical structures	Geranyl propionate Neryl propionate Citronellyl propionate
Constituent concentration range	50-65, 7-17, and 20-35%	Mono constituent
CAS no constituents	105-90-8, 105-91-9, and 141-14-0	105-87-3
EC number	906-089-0	203-341-5
REACH registration	Registered	Registered
Empirical formula	C13H22O2, C13H22O2, and C13H24O2	C12H20O2
Molecular weight	210, 210, and 212	196
Physico-chemical data
Physical state	Liquid	Liquid
Vapour pressure (Pa)	0.76 (measured)	1.3 (measured)
Log Kow	5.6 (measured)	4.04 (measured)
Water solubility (mg/L)	38 (measured)	29 (measured)
Human health endpoints
Skin irritation	Irritant (OECD TG 439)	Irritant (Woe, see ECHA site)
Eye irritation	Not irritant (OECD TG 438)	Not irritant (OECD TG 405)
Skin sensitisation	Read across	Sensitiser: EC3 is 13.7% (LLNA, OECD TG 429)

 

Justification for classification or non-classification

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).