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

Endpoint summary

Description of key information

Skin irritation corrosion and irritating, based on read-across from Citronellyl Acetate mono, tested in OECD TG 404 the substance is a skin irritant (Cat 2) .

Eye irritation: not irritating, based on read-across from Citronellyl Acetate mono tested in OECD TG 405.

Respiratory irritation: no adverse effects in absence of human data indicating such.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Irritation to skin and eye is assessed based on read-across from Citronellyl Acetate mono to Citronellyl Acetate Multi. The executive summaries of the source information are presented below followed by the read-across rationale.

Skin irritation of Citronellyl Acetate mono

An in vivo skin irritation test was performed with Citronellyl Acetate mono according to OECD 404 and following GLP principles. Three rabbits were exposed semi-occlusively to 0.5 mL of the test substance (purity 98.8%) during 4 hours. After exposure, the sites were washed with Lutrol and Lutrol in water (1:1), skins were examined at 1 hour, 24, 48, 72 hours, 8 and 15 days after patch removal. The mean erythema score (24 -72 hours) per animal was 3, 2.3 and 2.3 (highest score was 3, any erythema signs resolved on day 15), the mean edema scores were 1, 0.7 and 0.7 (any edema signs resolved at 72 hours). Scaling was observed in all animals 8 days after removal and scaling was still noted for one rabbit 15 days after removal. Based on these results, Citronellyl Acetate (‘mono’) is found to have skin irritant properties and is classified Category 2: Irritant to the skin.

Eye irritation of Citronellyl Acetate mono

An in vivo eye study was performed with Citronellyl Acetate mono according to OECD guideline 405 and following GLP principles. Three rabbits received a single instillation of 0.1 mL in the conjunctival sac of their right eyelid. No washing as performed, animals were observed at one hour after instillation and after 24, 48 and 72 hours. The scores for cornea opacity, conjunctiva effects (redness, swelling or discharge) and iris effects were 0 at all time-points for all rabbits. Based on these results, it is concluded that Citronellyl acetate (mono) has no eye irritant effects.

Respiratory irritation:

For respiratory irritation mostly human data are used for the assessment because no suitable in vitro or in vivo tests are available that can identify respiratory irritation. There are no human data such as indicated in R7.2.3 of the ECHA guidance that indicate respiratory reactions of the substance e.g. from consumer experience or occupational exposure. In addition, the substance is not corrosive or severely irritating which further minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2).

The skin and eye irritation of Citronellyl Acetate Multi using read across from Citronellyl Acetate mono (CAS# 150-84-5)

Introduction and hypothesis for the analogue approach

Citronellyl Acetate Multiis a multi-constituent. The main constituent of Citronellyl Acetate Multi isCitronellyl Acetate mono. It has an unsaturated hydrocarbon backbone to which an acetic ester is attached. The minor constituent is Dihydro-Citronellyl Acetate has the same structure except it has a saturated backbone.

For this substance no data on skin and eye irritation are available. In accordance with Article 13 of REACH, lacking information can be generated by means other than experimental testing, i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin and eye irritation of Citronellyl Acetate Multi, the analogue approach is selected because for the main constituent, Citronellyl Acetate mono, information on skin and eye irritation is available which can be used for read across.

Hypothesis: Citronellyl Acetate Multi has the same skin and eye irritation potential as Citronellyl Acetate mono being the key constituent of the Multi. The Dihydro-Citronellyl Acetate has the same potential based on similarities and structure.

Available information on skin irritation: For Citronellyl Acetate mono an in vivo skin irritation test was performed according to OECD 404 and following GLP principles. Three rabbits were exposed semi-occlusively to 0.5 mL of the test substance during 4 hours. After exposure, skins were examined at 1 hour, 24, 48, 72 hours, 8 and 15 days after patch removal. The mean erythema score (24 -72 hours) per animal was 3, 2.3 and 2.3 which result in assigning for skin irritation (all erythema gone after 15 days), the mean oedema scores were 1, 0.7 and 0.7 (all oedema was resolved at 72 hours). Scaling was observed on all animals 8 days after removal and scaling was still noted for one rabbit 15 days after removal. Based on the edema scores Citronellyl Acetate mono has skin irritant properties.

Available information on eye irritation: For Citronellyl Acetate mono an in vivo eye study was performed according to OECD guideline 405 and following GLP principles. Three rabbits received a single instillation of 0.1 mL in the conjunctival sac of their right eyelid. Animals were observed at one hour after instillation, and after 24, 48 and 72 hours. The scores for cornea opacity, conjunctiva (redness, swelling or discharge) or effects on iris were 0 at all time-points for all rabbits. Based on these results the substance is not an eye irritant.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemicals are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for acute dermal toxicity, of all substances.

Purity / Impurities

The purity and impurities of the target chemical do not indicate skin or eye irritation other than indicated by the parent substance. The impurities are all below < 10%.

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, which is presented below.

Analogue selection: For Citronellyl Acetate Multi the key constituent Citronellyl Acetate mono was selected for read across because for this substance reliable irritation is available. This information can be used for read across to Dihydro-Citronellyl Acetate.

Structural similarities and differences: Citronellyl Acetate Multi’s key constituent is Citronellyl Acetate mono. The information from the latter can be used for read across to Dihydro-Citronellyl Acetate because both are acetate esters of a 3,7-dimethyloctanol chain. The difference is that that Citronellyl Acetate mono has one double bond while Dihydro-Citronellyl acetate has a saturated alkyl chain.

Skin and eye absorption: Citronellyl Acetate Multi’s key constituent Citronellyl Acetate mono is expected to have the same skin and eye tissue absorption as Dihydro-Citronellyl Acetate based on similarity in chemical structure, MW and physico-chemical propertiesas presented in the Data matrix below.

Skin and eye reactivity:Citronellyl Acetate Multi’s key constituent Citronellyl Acetate mono is expected to have the same skin and eye reactivity compared to Dihydro-Citronellyl Acetate. If anything, the latter may be slightly less reactive based on the absence of a double bond in its alkyl hydrocarbon backbone.

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

Data matrix

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

Conclusions on skin and eye irritation

For Citronellyl Acetate Multi no skin and eye irritation information is available. Such information is available for the key constituent, which can be used for read across to Dihydro-Citronellyl Acetate the minor constituent, including adequate and reliable documentation.Citronellyl Acetate mono is considered a skin irritant but not an eye irritant and this will be used for read across.

Final conclusion: Citronellyl Acetate Multi is irritating to the skin (Skin irritant Cat. 2) and not irritating to the eye.

Data matrixpresenting the information relevant for read across toCitronellyl Acetate Multi from its key constituent Citronellyl Acetate mono and to Dihydro-Citronellyl Acetate for irritation

Substance	Citronellyl Acetate Multi	Citronellyl Acetate mono constituent	Dihydro-Citronellyl Acetate constituent
Read-across	Target	Source	Target
Structure *	See constituents
% in product	See constituents	60-75	10-20
CAS	See constituents	150-84-5	20780-49-8
EC number	908-114-0	205-775-0	244-034-6
REACH	Registered	Registered	Registered
MW	See constituents	198	200
Phys-chem
Appearance	Liquid	Liquid (ECHA site)	Liquid (ECHA site)
Log Kow	4.6 (exp.)	4.6 (ECHA site)	4.6 (ECHA site)
Ws (mg/L)	12.1 (exp.)	5.7 (ECHA site)	4.7 (ECHA site)
Vp (Pa)	2.6 (exp)	7.0(ECHA site)	12.9 (ECHA site)
Human health
Skin irritation	Skin irritant (RA)	Skin irritant (OECD 404)	Not a skin irritant (ECHA site)
Eye irritation	Not eye irritant (RA)	Not eye irritant (OECD 405)	Not an eye irritant (ECHA site)

RA = read-across.

 

Justification for classification or non-classification

The substance needs to be classified as Skin irritant Category 2, and shall be labelled with 'H315: Causes skin irritation', according to EU CLP (EC No. 1272/2008, and its amendments).

The substance does not need to be classified for eye irritation and respiratory irritation according to EU CLP (EC No. 1272/2008, and its amendments).