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

Endpoint summary

Description of key information

Acute oral toxicity: LD50 = 6800 mg/kg bw, based on read-across from Citronellyl Acetate mono tested in OECD TG 401

Acute dermal toxicity: LD50 >2000 mg/kg bw, based on read-across from Citronellyl Acetate mono tested in OECD TG 402

Acute inhalation: no adverse effect predicted, based on route to route extrapolation from read-across substance, Citronellyl Acetate mono

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute dermal toxicity result is of sufficient quality and adequate for this dossier.

Additional information

Acute oral toxicity is assessed based on read-across to Citronellyl Acetate Multi from Citronellyl mono. The executive summary of the source information is presented below followed by the read-across rationale.

Acute oral toxicity of Citronellyl Acetate mono

Oral acute toxicity data are available from a study comparable to OECD TG 401 with acceptable restrictions (Reliability 2). In this study 2 rats/sex were administered doses of 3000, 4600, 6800, and 10200 mg/kg bw via gavage (no vehicle) and observed for 14 days. Observations included mortality, clinical signs, and initial and final body weights. Necropsy of animals found dead during the test, and of survivors was performed. At doses of 6800 and 10200 mg/kg bw, mortality was 50% and 100%, respectively. At low doses hypoactivity and ruffed fur was recorded, at higher doses symptoms included also muscular weakness, prostration, and diarrhoea. No evident effect on body weights was observed in survivors. Post-mortem necropsy of survivors revealed no gross pathology. Animals found dead during the test showed gastroenteritis, pale livers, pale kidneys, and haemorrhages in the stomachs. Based on these findings, the acute oral LD50 is 6800 mg/kg bw in male and female rats.

Acute inhalation toxicity calculated

Acute inhalation is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2015, 3.1.3.3.4: 1 mg/kg bw = 0.0052 mg/l (5.2 mg/m3). The acute inhalation is predicted to be: LC50=5000 x 5.2 x 100/100 = 35360 mg/m3 (using 100% inhalation and 100% oral absorption). The calculated saturated vapour pressure is ca. 207 mg/m3 (MW*VP/ 8.3 (gas constant)*298K). This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation is anticipated.

Acute dermal toxicity of Citronellyl Acetate mono

Dermal acute toxicity data are available from a study comparable to OECD TG 402 with acceptable restrictions (Reliability 2). In this study 2 rabbits/sex were administered a single dose of 2000 mg/kg bw (undiluted test material) on shaved skin wrapped in an occlusive material. Exposure duration was 24 hours followed by a 14-day observation period. Examinations included mortality, initial and final body weight, behavioural abnormalities, and skin reactions. Necropsy of animals found dead during the test, and of survivors was performed. No mortality or other signs of toxicity were observed throughout the test. Local skin reactions included definite red erythema and mild edema after 24 h, superficial escharosis after 6 days, and sloughing at end of the 14-day observation period. Based on these findings, the acute dermal LD50 is >2000 mg/kg bw in male and female rats.

The acute oral and dermal toxicity 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 which is very similar, only the backbone is saturated.

For this substance no acute oral and dermal toxicity data are available. In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral and dermal toxicity of Citronellyl Acetate Multi the analogue approach is selected because for the main constituent, Citronellyl Acetate mono, acute oral and dermal toxicity information is available which can be used for read-across.

Hypothesis: The acute oral and dermal toxicity of Citronellyl Acetate Multi is the same as is of Citronellyl Acetate mono because this is the key constituent of the Multi. Dihydro-Citronellyl Acetate acute toxicity will be similar bases on similarity in alkyl backbone, the same acetate functional group and being a minor constituent.

Available information for acute oral: For Citronellyl Acetate mono acute oral toxicity data are available from a study comparable to OECD TG 401 with acceptable restrictions (Reliability 2). In this study 2 rats/sex were administered doses of 3000, 4600, 6800, and 10200 mg/kg bw via gavage (no vehicle) and observed for 14 days. The acute oral LD50 is 6800 mg/kg bw in male and female rats.

Available information on acute dermal:toxicity data are available for Citronellyl Acetate mono from a study comparable to OECD TG 402 with acceptable restrictions (Reliability 2). In this study 2 rabbits/sex were administered a single dose of 2000 mg/kg bw (undiluted test material) on shaved skin wrapped in an occlusive material. Exposure duration was 24 hours followed by a 14-day observation period. The acute dermal LD50 is >2000 mg/kg bw in male and female rats.

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 oral and dermal toxicity.

Purity / Impurities

The purity and impurities of the target chemical do not indicate acute oral toxicity potential 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 its key constituent Citronellyl Acetate monowas used as data source because it is the main constituent and for this substance acute oral and dermal toxicity information is available. This information can be used to read across to Dihydro-Citronellyl Acetate based on chemical structure similarity.

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.

Toxico-kinetic: Absorption: Similarity in chemical structure and physico-chemical properties of both constituents of Citronellyl Acetate Multi indicates similar absorption behaviour. These constituents have similar molecular weights (196 to 200 g/mole) and log Kow values (4.6 to 5.0) favourable for uptake via the oral and dermal route.

Metabolism: The ester bond present in the acetate ester of both key constituent of Citronellyl Acetate Multi is expected to behydrolysed/cleaved by carboxyl esterases in the gut and liver into the respective alcohol and acetic acid rapidly as based on Geranyl acetate metabolism among others (Saghir et al. 1997 and toxico-kinetic section). The oxidation and/or hydrolysation of the hydrocarbon backbone of the unsaturated Citronellyl Acetate mono will be similar to that of the saturated Dihdro-Citronellyl Acetate predicted by OECD Toolbox rat metabolism simulator. The ester can turn into an alcohol, aldehyde and finally an acid for both. The methyl group can be hydroxylised in both. According to the Toolbox the double bond in the tail will not be hydroxylised but it can happen in the saturated tail. This latter is step is considered a minor metabolisation step. In Annex 1 the metabolites are depicted.

Toxico-dynamics: The reactivity of the similar metabolites will present similar toxicity.

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

Data matrix

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

Conclusions on acute oral and dermal toxicity

For Citronellyl Acetate Multi no acute oral and dermal toxicity information is available. For the main constituent Citronellyl Acetate mono such information is available which can be used for read across to Dihydro-Citronellyl Acetate (the minor constituent) and this read across is adequately and reliably presented in the current document.Citronellyl Acetate mono, reliable acute oral and dermal toxicity data is available with LD50 values of 6800 mg/kg bw and >2000 mg/kg bw, respectively.These data can be used directly for read-across to Citronellyl Acetate Multi.

Final conclusion:For Citronellyl Acetate Multi the acute oral and dermalLD50 values are >5000 mg/kg bw and >2000 mg/kg bw,based on read-across.

References:

Saghir. M., Werner, J., Laposta, M., 1997, Rapid in vivo hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol metabolites, Am. J. Physiol., 273, G184-G190.

Data matrixpresenting the information relevant for read across toCitronellyl Acetate Multi from Citronellyl

Acetate mono for acute toxicity

Substance	Citronellyl Acetate Multi	constituent	constituent
Read-across	Target	Source	Target
Chemical name	--	Citronellyl Acetate mono	Dihydro-Citronellyl Acetate
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 (SSS dossier)
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
Acute oral Mg/kg bw	LD50 >5000 (RA)	LD50 >5000 (OECD TG 401)	LD > 5000 (ECHA site)
Acute dermal mg/kg bw	LD50 >2000 (RA)	LD50 >2000 (OECD TG 402)	LD = 5000 (ECHA site)

RA = read-across.

 

 

Annex 1 OECD Toolbox metabolic prediction for Citronellyl Acetate mono (5 metabolites, first row and of Dihydro-Citronellyl Acetate (6 metaoblites, next two rows). The additional metabolite is the hydroxylation of the tail-isoprene group.

 

Citronellyl Acetate mono

 

Dihydro-Citronellyl Acetate metabolites

 

 

 

 

Justification for classification or non-classification

The substance does not need to be classified for acute toxicity by the oral, inhalation and dermal route according to EU CLP (EC No. 1272/2008, and its amendments).