Rosetal A

Endpoint summary

Description of key information

Skin sensitisation: The substance is a skin sensitiser (1B) based on read across from the constituent Geraniol tested in an OECD TG 429 (EC3=11.4%).

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

First data from 3 HRIPT studies with Rosetal A are presented. Next the executive summary on the LLNA of the constituent Geraniol (used as key information) is shown and thereafter the justification for using this data for assessing the skin sensitisation potential for Rosetal A.

Three HRIPT assays were performed by IFF: 0/43, 0/42, and 0/104 subjects showed sensitisation when exposed to 0.5% (1965), 1.25% (1965), and 1.5% (2014) Rosetal A, respectively, these data are presented below. No other information on Rosetal A was found.

HRIPT study 1965 - TTC-0153-A - 0.5% Rosetal A

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.5 ml, test concentration used was 0.5% and the applied surface was 2.5 cm2. During the induction patches were placed on the upper arm. The subjects removed the bandages 24 hours after application. The reaction of each exposure was scored at the following session and the reaction to the ninth application on Monday of the fourth week. On Monday of the sixth week a challenge patch was applied to a site not previously exposed and removed after 24 hours. Reactions to the challenge were scored on Wednesday and Friday of this week. None of the subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used.

HRIPT study 1965 – 3TC-0153-R - 1.25% Rosetal A

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.5 ml, test concentration used was 1.25% and the applied surface was 2.5 cm2. During the induction patches were placed on the upper arm. The subjects removed the bandages 24 hours after application. The reaction of each exposure was scored at the following session and the reaction to the ninth application on Monday of the fourth week. On Monday of the sixth week a challenge patch was applied to a site not previously exposed and removed after 24 hours. Reactions to the challenge were scored on Wednesday and Friday of this week. None of the 42 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used.

HRIPT study 2014 – 13-217C-01 - 1.5% Rosetal A

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.2 ml, test concentration used was 1.5% and the applied surface was 3.63 cm2. During the induction patches were placed on the upper back. Technicians removed the patches 24 hours after application, except for Saturdays on which the patients removed the patches themselves. After removal, 24 hours the skin was not treated, except for the 48 hours treatment free period after the Friday application. Two weeks after the final induction treatment, a challenge patch was applied to a previously untreated site on the back and removed after 24 hours. Reactions to the challenge were assessed after 24, 48, 72 and 96 hours. None of the 104 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration

Local Lymph Node Assay (OECD TG 429) of Geraniol

This Local Lymph Node Assay (OECD TG 429) was performed to determine the sensitising potential of the substance in mice. Groups of 4 mice were treated with test concentrations of 2.5, 5, 10, 25 and 50% w/v ethanol:diethyl phthalate 1:3, or a vehicle treated control. Hexylcinnamaldehyde (HCA), freshly prepared as 1, 3 and 10% w/v dilution in acetone, was used as positive control. Clinical observations and bodyweights were recorded, and lymph node proliferation was determined using 3HTdR incorporation.

The number of radioactive disintegrations per minute (dpm) reflect the proliferation response of lymph node cells, and were 330, 574, 800, 926, 1582 and 2000 dpm/lymph node for the vehicle control, 2.5%, 5%, 10%, 25%, and 50% concentration groups, respectively. This corresponds with a lymph node proliferation of n.a., 1.74, 2.42, 2.81, 4.79 and 6.06, respectively, for the substance-treated groups, calculated as the Stimulation Index (SI). This SI was greater than 3-fold at the 25% and 50% w/v concentrations. An EC3 value of 11.4% was calculated. 

The justification for the read across to Geraniol is attached in a target study record.

 

Rosetal A and its skin sensitising properties using data from the constituent Geraniol

Rosetal A is a reaction product with several constituents. For this substance as such no skin sensitisation information is available which fulfil the Annex VII requirements. All constituents of Rosetal A > 1% are presented in Annex 1. Several constituents have skin sensitisation data which can be used for assessing Rosetal A’s skin sensitisation potential. This information is used in accordance with Article 13 of REACH where it is said that lacking information can be generated by other means, i.e., applying alternative methods such as in vitro tests, SARs, grouping, read-across or using constituents of the substance with relevant sensitisation data.

Hypothesis: The skin sensitisation of Rosetal A can be predicted with Geraniol, which is a constituent of Rosetal A.

Available information:  For Rosetal A, three HRIPT assays were performed in which 0/43, 0/42, and 0/104 subjects showed sensitisation when exposed to 0.5% (1965), 1.25% (1965), and 1.5% (2014) Rosetal A, respectively. For 5 constituents skin sensitisation data can be derived from the disseminated ECHA dossiers (see Annex 1 for reference):

- Block 0 2‐phenylacetaldehyde: Classified as Category 1B (OECD 429, 2001) with an EC3 of 3.0%.

- Block 1 (2,2‐dimethoxyethyl)benzene: Not sensitising (OECD 429, 2015)

- Block 2 Citronellol: Classified as Category 1B (OECD 429, RIFM, 2005) with an EC3 of 43.5%.

- Block 2 Nerol: Classified as Category 1B (OECD 429, DRT, 2013) with an EC3 of 23%.

- Block 2 Geraniol: Classified as Category 1B (OECD 429, RIFM, 2003) with an EC3 of 11.4%.

- Block 3 all substances: no data

- Block 4 all substances: no data

Constituents

Chemical structures of Rosetal A’s constituents are shown in Annex 1 including molecular weight and log Kow

Purity / Impurities.

Rosetal A has a purity of > 90%. All constituents of > 1% are presented in Annex 1.

Constituent approach justification

A constituent approach is used to assess skin sensitisation potential. When using the constituent approach, the result derived should be applicable for classification and labelling and/or risk assessment and it should be presented with adequate and reliable documentation, which is presented below.

Constituent selection: For Rosetal A several constituents show skin sensitisation potential. Geraniol is selected as key constituent for pragmatic reasons.

Toxico-kinetics: The constituents with the lower molecular weight (block 0, 1 and 2) can be absorbed dermally to some extent, which for the constituents of block 3 and 4 this is more limited due to higher molecular weights and log Kow of these latter blocks. Therefore, it is justified to use Geraniol belonging to block 2 as the key constituent for assessing this endpoint for a conservative assessment.

Toxico-dynamics: For Rosetal A the constituent Geraniol is the key representative. Its mode of action is due to the alpha-beta conjugated alcohol bond and/or sensitisation may be due to oxidation of the double bond in the tail. The constituents with a conjugated acetal bond (block 3 and 4) are conservatively predicted to have similar reactivity and all have the double bond in the tail as Geraniol has.

Uncertainty of the prediction: Rosetal A contains constituents with low concentration in the whole multi-constituent but with skin sensitisation potential. The main constituents (with higher concentrations) have lower dermal absorption but may also present sensitisation because of skin sensitisation alerts in their chemical structure. The constituent 2-phenylacetaldehye in block 0 has an EC3 of 3% which is lower compared to Geraniol, which has an EC3 of 11.4%. The concentration of this 2-phenylacetaldehyde is 1.26% , while for Geraniol it is 5.46%. Based on these concentration differences between these two, Geraniol can also cover the sensitisation potential of 2-phenylacetaldehyde. Using Geraniol EC3 is considered conservative because constituents of Rosetal A of Blocks 3 and 4 are expected to have a lower skin sensitisation potential based on their lower dermal absorption characteristics such as higher molecular weights and log Kow.

Conclusion on skin sensitisation potential

For Rosetal A no skin sensitisation data are available which can cover the endpoint for REACH. There are several constituents in this substance, which have skin sensitisation data which can be extrapolated to Rosetal A. Geraniol is selected as key constituent. The justification for this constituent approach is presented above. On this basis the Rosetal A EC3 can be derived from Geraniol, which has an EC3 of 11.4%.

Final conclusion: Rosetal A has an EC3 of 11.4%.

Annex 1: Structural information

	Name	CAS	%	Structure	MW	Log Kow	ECHA reference
Block 0	2‐phenylacetaldehyde	122-78-1	1.26		120	1.44 (25^◦C, OECD TG 117)	Information available in ECHA disseminated dossier
Block 1	(2,2‐dimethoxyethyl)benzene	101-48-4	13.10		166	2.23 (24.7^◦C, OECD TG 117)	Information available in ECHA disseminated dossier
Block 2	3,7‐dimethyloct‐6‐en‐1‐ol (Citronellol)	106‐22‐9	3.04		156	3.41 (25^◦C, EC A.8)	Information available in ECHA disseminated dossier
Block 2	(Z)‐3,7‐dimethylocta‐2,6‐dien‐1‐ol (Nerol)	106-25-2	1.46		154	Ca. 2.76 (30^◦C, EC A.8)	Information available in ECHA disseminated dossier
Block 2	(E)‐3,7‐dimethylocta‐2,6‐dien‐1‐ol (Geraniol)	106-24-1	5.43	See Z-isomer above	154	2.6 (25^◦C, OECD TG 117)	Information available in ECHA disseminated dossier
Block 3	(2‐((3,7‐dimethyloct‐6‐en‐1‐yl)oxy)‐2‐methoxyethyl)benzene		10.91		290	6.12 (Episuite)	-
Block 3	(Z)‐(2‐((3,7‐dimethylocta‐2,6‐dien‐1‐yl)oxy)‐2‐methoxyethyl)benzene		5.05		288	6.03 (Episuite)	-
Block 3	(E)‐(2‐((3,7‐dimethylocta‐2,6‐dien‐1‐yl)oxy)‐2‐methoxyethyl)benzene		19.10	See Z-isomer above	288	6.03 (Episuite)	-
Block 4	{2,2‐bis[(3,7‐dimethyloct‐6‐en‐1‐yl)oxy]ethyl}benzene		6.30		414	10.31 (Episuite)	-
Block 4	(E)‐(2‐((3,7‐dimethyloct‐6‐en‐1‐yl)oxy)‐2‐((3,7‐dimethylocta‐2,6‐dien‐1‐yl)oxy)ethyl)benzene		17.19		412	10.22 (Episuite)	-
Block 4	(2,2‐bis(((E)‐3,7‐dimethylocta‐2,6‐dien‐1‐yl)oxy)ethyl)benzene	67634‐02‐0	11.57		410	10.14 (Episuite)	-

 

Justification for classification or non-classification

The substance is a skin sensitiser (1B) based on read across from the constituent Geraniol tested in an OECD TG 429 and shall be labelled with H317: May cause an allergic skin reaction according to EU CLP (EC No. 1272/2008 and its amendments).