2-phenylpropionaldehyde-dimethyl acetal

Endpoint summary

Description of key information

Skin sensitisation: the substance is not a skin sensitiser based on read across from Phenylacetaldehyde Dimethyl Acetal, which was tested in an LLNA (OECD TG 429, GLP)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

For Hydratropic Ald DMA, skin sensitising properties are derived from the close structural analogue Phenylacetaldehyde Dimethyl Acetal. The summary of the experimental information is presented first and thereafter the read across rationale.

Skin sensitisation of Phenylacetaldehyde Dimethyl Acetal

In a local lymph node assay, performedaccording to OECD Guideline 429 and GLP, fourgroups of 5 CBA/Jcr female mice were treated on the dorsal surface of both ears once per day for 3 days with 25%, 50% or 100% (v/v) of the test substance or the vehicle alone (acetone/olive oil in a ratio of 4:1). In addition, 5 animals were treated similar with alpha-hexylcinnamaldehyde as positive control. Five days after the first topical application of the test material, the mice were injected intravenously with 3H-methyl thymidine in phosphate buffered saline. Five hours later, the mice were euthanized and the draining auricular lymph nodes were removed. The lymph node cells were precipitated with 5% trichloroacetic acid (TCA) and the pellets counted in a scintillation counter to determine incorporation of the 3H-thymidine. Exposure to the test substance at 25, 50 and 100% (v/v) resulted in stimulation indices of 2.97, 1.84, and 2.39. For the positive control, an EC3 of 13.3 was calculated, showing the validity of the test. Therefore, the test material is considered to be a non-sensitiser under the conditions of the test.

Hydratropic Ald DMA (Cas no.: 90-87-9) and its absence ofsensitising properties are based on read across from Phenylacetaldehyde Dimethyl Acetal (CAS no.: 101-48-4)

Introduction and hypothesis for the read across

Hydratropic Ald DMA is an ethylbenzene with a methyl-group attached to the first position of the ethyl-group and a dimethyl acetal attached to the second position. For this substance no experimental skin sensitisation data is available. In accordance with Article 13 of REACH where is presented thatlacking information can be generated by means other than experimental testing such as in vitro tests, SARs, grouping and read-across, the data gap of Hydratropic Ald DMA is filled by using read across from the analogue Phenylacetaldehyde Dimethyl Acetal.

Hypothesis: Hydratropic Ald DMA is expected to have no sensitizing propertiesbased on the negative results of the analogue Phenylacetaldehyde Dimethyl Acetal.

Available information: For Phenylacetaldehyde Dimethyl Acetal a well conducted LLNA (OECD TG 429, Klimisch 1) is available. The obtained data indicate that the substance has no skin sensitisation properties.

Target and Source chemical(s):

Chemical structures of the target chemical and the source chemicals and relevant information on these substances are shown in the data matrix.

Purity / Impurities:

Hydratropic Ald DMA is a mono-constituent with a purity of 98.4% and all impurities are < 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 Hydratropic Ald DMA the structural close analogue Phenylacetaldehyde Dimethyl Acetal is selected for read across.

Structural similarities and differences: Hydratropic Ald DMA and Phenylacetaldehyde Dimethyl Acetal have the same backbone and functional group (acetal). They are both ethylbenzenes with a dimethyl acetal attached. The difference is an additional methyl group attached to the ethyl-group of Hydratropic Ald DMA. This additional carbon methyl group does not add or reduce the reactivity of the acetate.

Dermal absorption: Hydratropic Ald DMA and Phenylacetaldehyde Dimethyl Acetal are both liquids and have similar molecular weight. Also, the physico-chemical properties such as log Kow (3 and 2.23, respectively) indicate that these substances will be absorbed by the skin to a similar extent.

Skin sensitisation reactivity: Hydratropic Ald DMA and Phenylacetaldehyde Dimethyl Acetal both have two ethers (acetal) as a functional group and therefore are expected to have the same reactivity. In view of the additional carbon methyl group not influencing the reactivity of the acetal group: very slight protrusive effect and no electron withdrawing effect, both substances will have the same skin sensitisation potency. For support OECD Toolbox present no alert for protein binding for both substances. Somewhat in contrast, Derek Nexus predicts 17 and 34% potential EC3, because both substances can be aldehyde precursors. This aldehyde formation is not expected, because Phenylacetealdehyde Dimethyl Acetal was not positive in the LLNA.

Other reactivity endpoints: The absence of reactivity is further supported with the absence of skin and eye irritation properties of both substances.

Remaining uncertainties: There are no other remaining 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 below.

Conclusions for skin sensitisation 

For Hydratropic Ald DMA no skin sensitisation information is available but for the structural analogue Phenylacetaldehyde Dimethyl Acetal such information is. 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. For Phenylacetaldehyde Dimethyl Acetal reliable data are available from a LLNA, showing no skin sensitisation potential. This information can be used for read-across to Hydratropic Ald DMA.

Final conclusion: Hydratropic Ald DMA is not a skin sensitiser.

Data matrix: Information on Hydratropic Ald DMA and Phenylacetaldehyde Dimethyl Acetal for assessment of skin sensitization

Common names	Hydratropic Ald DMA Target	Phenylacetaldehyde Dimethyl Acetal Source
Chemical structures
Chemical name	2-phenylpropionaldehyde-dimethyl acetal	1,1-dimethoxy-2-phenylethane
CAS no.	90-87-9	101-48-4
EC no.	202-022-8	202-945-6
Empirical formula	C11H16O2	C10H14O2
Molecular weight	180.25	166.22
Phys-Chem
Physical state	Liquid	Liquid
Water solubility (mg/L)	3484 at 24°C	3900 at 20°C
Log Kow (measured)	3 (OECD TG 117)	2.23 (OECD TG 117)
Human health
Skin sensitisation	RA Phenylacetaldehyde Dimethyl Acetal	Not sensitising (OECD 429)
Skin irritation	Not irritating (OECD TG 439	Not irritating (OECD 439)
Eye irritation	Not irritating (OECD TG 437	Not irritating (OECD 405)

Justification for classification or non-classification

The substance is not a skin sensitiser and therefore it does not need to be classified for skin sensitisation according to EU CLP (EC 1272/2008 and its amendments).