Reaction mass of 3,7-dimethyl-1-octyl propionate and citronellyl propionate

Endpoint summary

Description of key information

Skin sensitisation potential is based on read across from Citronellyl butyrate which is tested in an LLNA type of test OECD TG 442B 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 potential of Citronellyl Propionate is based on read-across from Citronellyl Butyrate. The executive summary of the skin sensitisation results of the latter are presented below and are followed by the read-across rationale.

Skin sensitisation information from Citronellyl Butyrate

In a Local Lymph Node Assay (BrdU-ELISA), the skin sensitisation potential of the substance was tested according to OECD TG 442B test guideline and GLP principles. Per concentration, 5 female mice were used. Skin sensitization potential was evaluated by ear thickness measurements. Cellular proliferations and SI were determined. In the first set, at 25, 50 and 100%, SI values were 1.78, 2.15 and 1.70, respectively. In the second set, at 1, 5 and 10%, SI values were 1.22, 1.10 and 1.40, respectively. Negative and positive controls were included and all acceptability criteria were met (SI values positive controls: 3.10 and 4.32). These results show that the substance could elicit a SI ≥ 1.6. An EC1.6 value of 26.4% was calculated. Based on the results, the substance is considered a skin sensitiser.

Citronellyl propionate’s (EC no. 907-873-5) sensitising properties are based on read across from Citronellyl butyrate (Cas no. 141-16-2 )

Introduction and hypothesis for the read across

Citronellyl 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 Citronellyl propionate is filled by using read across from the analogue Citronellyl butyrate.

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

Available information: For Citronellyl butyrate a well conducted LLNA BRDU test (OECD TG 442B, Kl. 1) is available and an EC1.6 of 26.4% was found. These data shows that the substance has skin sensitisation properties.

Target and Source chemical(s):

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

Purity / Impurities:

Citronellyl propionate is a multi-constituent containing two similar isomers: Citronellyl propionate (70-90%) and 3,7-dimethyloctyl propanoate (5-25%). 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 Citronellyl propionate the analogue Citronellyl butyrate 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: Citronellyl propionate and Citronellyl butyrate have the same backbone and the same functional ester group. The difference is that the minor constituent 3,7-dimethyloctyl propanoate has one double bond less in the backbone. Another difference is the propionate versus the butyrate group of the analogue: the latter substance has one methyl group extra in the alkyl chain.

Dermal absorption: Citronellyl propionate and Citronellyl butyrate are both liquids and have similar molecular weights. Also the physico-chemical properties such as log Kow (5.6 and 6.2, respectively) indicate that these substances will be absorbed by the skin to a similar extent.

Skin sensitisation reactivity: Citronellyl propionate and Citronellyl butyrate have the same reactivity because of the double bond in the tail and therefore the same skin sensitisation potential is anticipated. The minor constituent does not have a double bond in the tail and is therefore less reactive. The non-skin and eye irritation in 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 Citronellyl propionate no skin sensitisation information is available but for Citronellyl butyrate such information is available and this can be used to fill the data gap of Citronellyl 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 Citronellyl butyrate reliable data are available from a LLNA BRDU test (OECD TG 442B), showing an EC1.6 of 26.4%, showing skin sensitisation as is presented in the current document. This information can be used for read across to Citronellyl propionate.

Final conclusion: Citronellyl propionate has an EC1.6 of 26.4 and is therefore is a skin sensitiser.

Data matrix of Citronellyl propionate (target) and Citronellyl butyrate (source) to support the skin sensitising potential of the target

Common names	Citronellyl propionate	Citronellyl butyrate
	Target	Source
Chemical structures	Citronellyl propionate 3,7-dimethyloctyl propanoate
Constituent concentration range	70-90 and 5-25%	Mono constituent
CAS no	141-14-0 and 93804-81-0	141-16-2
EC number	907-873-5	205-463-4
REACH registration	Registered	Registered
Empirical formula	C13H24O2 and C13H26O2	C14H26O2
Molecular weight	212 and 214	226
Physico-chemical data
Physical state	Liquid	Liquid
Vapour pressure (Pa)	1.0 (measured)	10 (Measured)
Water solubility (mg/l)	5.1 (measured)	1.63 (measured)
Log Kow	5.6 (measured)	6.2 (measured)
Human health endpoints
Skin irritation	Not irritant (OECD TG 439)	Not irritant (OECD TG 439)
Eye irritation	Not irritant (OECD TG 438)	Not irritant (OECD TG 437 and 492)
Skin sensitisation	Read across	Sensitiser: EC1.6 is 26.4% (LLNA BRDU, OECD TG 442B)

 

 

 

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).