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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation using read across from Cyclamen aldehyde (tested in OECD TG 429): EC3 22.3%: skin sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Information is retrieved from read across
Justification for type of information:
The read across documentation is presented in the Sensitisation Endpoint summary, the accompanying documents are also attached there.
Reason / purpose for cross-reference:
read-across source
Key result
Key result
other: NOEC / %
Remarks on result:
other: Vehicle control
Remarks on result:
other: Test group 1%
Remarks on result:
other: Test group 2.5%
Remarks on result:
other: Test group 10%
Remarks on result:
other: Test group 25%
Remarks on result:
other: Test group 50%
Interpretation of results:
other: Skin sensitisation 1B
according to EU CLP (EC1272/2008 and its updates)
Substance is considered to have an EC3 of 22.3% and therefore a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A HRIPT study in which Floralozone is tested at 3.5% is available. This information is considered insufficient to fulfil the REACH requirements. Therefore LLNA information from Cyclamen aldehyde (CAS #103-95-7) is used for read across to Floralozone. In this section first the LLNA of Cyclamen aldehyde is summarised, thereafter the HRIPT study with Floralozone and finally the full read across justification.

Cyclamen aldehyde (103 -95 -7) LLNA (OECD TG 429

The skin sensitisation potential of the substance has been tested in a study similar to OECD TG 429: Local Lymph Node Assay method. At 1, 2.5, 10, 25 and 50% were 1.4, 1.34, 1.84, 3.26 and 5.16, respectively. Reliable negative control was included. The test substance could elicit a SI ≥ 3. An EC3 has been derived resulted in an EC3 of 22.3%.A NOEC of 10% is derived. Based on the results, the substance was considered to be a sensitiser.

HRIPT (with Floralozone)

One hundred twelve subjects participated in evaluating the potential of 3.5% w/w test material in EtOH:DEP (1:3) to elicit dermal irritation and/or induce sensitization. The test material was applied under an occlusive patch to the upper back of each subject and was allowed to remain in direct skin contact for a period of 24 hours. Patches were applied to the same site for a total of 9 applications during the Induction Period. The sites were graded for dermal irritation 24 hours after removal of the patches and 48 hours after removal. Following a 2-week rest period, challenge patches were applied to previously untreated test sites on the back. After 24 hours, the patches were removed and evaluated. The test sites were re-evaluated at 48 and 72 hours. One hundred eight subjects completed the study. The test material did not demonstrate a potential for elicit dermal irritation or sensitization under the test conditions.

Assessing the sensitisation potential of Floralozone (CAS #67634-14-4 and #67634-15-5) using Cyclamen aldehyde (CAS #103-95-7)

Introduction and hypothesis for the analogue approach for skin sensitisation

Floralozone is an ethyl substituted phenyl-propyl aldehyde,to which a dimethyl group is attached to the alpha position.In accordance with Article 13 of REACH, lacking information can be generated by applying alternative methods such asin vitrotests, QSARs, grouping and read-across. In this case read across will be used for assessing the skin sensitising potential of Floralozone using Cyclamen aldehyde as an analogue. This analogue has a similar molecular structure compared to Floralozone and therefore information from Cyclamen aldehyde can be used to determine the skin sensitising potential of Floralozone (see data matrix).

Hypothesis:Floralozone (target) has similar sensitisation potential compared to Cyclamen aldehyde (source) resulting in a similar skin sensitising effect because both molecular structures are similar.

Available information:For Floralozone aHRIPT test with 3.5% substance is available. In this study no skin sensitisation was observed, the REACH requirements cannot be fulfilled with this information. For the analogue Cyclamen aldehyde a Local Lymph Node Assay is available which result can be used forFloralozone. The assay was performed equivalent to OECD TG 429: Local Lymph Node Assay method. The study was assigned reliability 1.

2. Target chemical and source chemical(s)

Chemical structures of the target and the source are shown in the data matrix (see also the attached document in IUCLID section 7.4).

3. Purity / Impurities

Floralozone contains two constituents that are isomers, where CAS# 67634-15-5 (para) is present at 60-75% and CAS# 67634-14-4 (ortho) is present at 20-30%. Cyclamen aldehyde contains one main constituent present at ca. 100%.As a result it is not expected that the impurities of the source and target chemicals affect the read-across justification.

4. 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.

Structural similarities and differences:Floralozone and Cyclamen aldehyde have the same phenyl-propyl aldehyde backbone and the same functional group: the aldehyde. The difference is that Floralozone has two methyl groups on the alpha position next to the aldehyde and Cyclamen aldehyde has one. Floralozone has an ethyl group on the para-position of the phenyl group while Cyclamen aldehyde has an isopropyl group. These differences are not expected to have a different skin sensitisation potential. Also the para versus the ortho position of the ethyl group in Floralozone is not expected to make a difference in skin sensitisation potential.

Toxico-kinetic similarities and differences:For skin sensitisation the dermal absorption is of secondary importance. Cyclamen aldehyde has a very similar log Kow compared to Floralozone: 3.9 and 4.1, respectively.

Toxico-dynamic aspect: Reactivity:Floralozone and Cyclamen aldehyde contain the same reactive groups and no difference in reactivity is to be expected. 

Experimental data similarity and difference:The skin and eye irritation endpoints are other local endpoints for which reactivity is a key parameter. Both substances are irritating to the skin and not irritating to the eyes supporting the similarity in reactivity.

Uncertainty of the prediction:There is no remaining uncertainty, in view of similarities in structure, and reactivity, as presented above the read across is justified.

5. Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data matrix in Table 1.

6. Conclusions per endpoint for C&L and dose descriptor

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.

Cyclamen aldehyde is an analogue for Floralozone. Cyclamen aldehyde is a skin sensitizer in an LLNA test and has an EC3 of 22.3 and a NOEC of 10%. In view of the close similarity with Floralozone the same values can be used.

Final conclusion on hazard, C&L and risk characterization:

Floralozone has EC3 of 22.3 and a NOEC of 10% based on analogue information. Therefore it has to be classified for skin sensitization and a NOEC will be used for the risk characterization.

Data matrix for assessing the skin sensitisation of Floralozone using read across from Cyclamen aldehyde

Common names


Cyclamen aldehyde

Chemical structures

CAS no

67634-14-4 and 67634-15-5



O=CC(Cc1c(cccc1)CC)(C)C and O=CC(Cc1ccc(cc1)CC)(C)C


Molecular weight






Physico-chemical data



Melting point, °C



Boiling point, °C



Vapour pressure, Pa



Water solubility, mg/l



Log Kow



Human health



Skin irritation/corrosion

irritating (OECD 439)

irritating (similar to OECD 404)

Eye irritation/corrosion

not irritating (OECD 438)

not irritating (similar to OECD 405)

Skin sensitisation

EC3 derived by read across

Skin sensitiserEC3 of 22.3%.

(OECD TG 429)


HRIPT: 3.5% no sensitisation




Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The substance is not a respiratory sensitizer because there are no human data that indicate respiratory sensitisation. In addition the potential for respiratory sensitisation of the substance is assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-2).

1)           The substance is a moderate skin sensitizer;

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

3)           The substance has not structural alerts or is structurally related to chemicals causing respiratory sensitization as presented in Table R.7.3-1 in the ECHA guidance of 2008 or those provided in the following document:

Using this ITS in the ECHA guidance it can be concluded that the substance is not a respiratory sensitizer.

Justification for classification or non-classification

According to EU CLP (EC No. 1272/2008 and its updates) the substance is classified as a skin sensitiser category 1B with the following H phrased: H319: May cause an allergic skin reaction. The substance does not need to be classified and labelled when using the information on respiratory sensitisation in accordance with EU CLP (Regulation (EC) No. 1272/2008 and its updates).