3,7-dimethylocta-2,6-dienyl acetate

Endpoint summary

Description of key information

Acute oral toxicity for Neryl acetate multi: LD50 >4555 mg/kg bw (based on read-across from Neryl Acetate mono tested in an OECD TG 401)

Acute dermal toxicity for Neryl acetate multi: LD50 > 5466 mg/kg bw (based on read-across from Neryl Acetate mono tested in an OECD TG 402)

Acute inhalation for Neryl aceate multi (oral to inhalation route extrapolation): LC50 > 11843 mg/m3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Additional information

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

Acute oral toxicity of Neryl acetate mono:

The oral acute toxicity of Neryl Acetate mono was investigated in a study comparable to OECD TG 401 (non-GLP). In this study, 5 male and 5 female rats were administered a single oral dose of 5 mL (4555 mg/kg bw based on a relative density of 0.911) by gavage followed by a 14-day observation period. No mortality or other signs of toxicity were observed throughout the test. No clinical signs were noted. Based on these findings, the acute oral LD50 of Neryl acetate mono was determined to be >4555 mg/kg bw.  

Acute inhalation toxicity Neryl acetate multi:

Acute inhalation is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2017, 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 = 4555 x 5.2 x 50/100 = 11843 mg/m3 (using 100% inhalation and 50% oral absorption). The calculated saturated vapour pressure is 170 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 Neryl acetate mono:

The dermal acute toxicity of Neryl acetate mono was investigated in a study comparable to OECD TG 402 (non-GLP). In this study, three groups of 4 rabbits were administered dermal doses of 2, 3.9, or 6.0 mL (1822, 3553, and 5466 mg/kg bw based on a relative density of 0.911) for 24 hours on intact and abraded skin, followed by a 14-day observation period. Treated skin was covered with a rubber sleeve or dam (occlusive exposure). Examination of treated skin after 24 hours, showed no signs of erythema or oedema, and remained normal during the 14-day observation period. No test item-related effects on feeding, body weight or behaviour were recorded. Haematology and urinalysis revealed no significant changes. No mortalities occurred. Based on these findings, the acute dermal LD50 of Neryl acetate mono was determined to >5466 mg/kg bw.  

The acute oral and dermal toxicity of Neryl acetate multi using read across from Neryl acetate mono (CAS# 141-12-8)

Introduction and hypothesis for the analogue approach

Neryl acetate multi is a multi-constituent of Neryl acetate and Geranyl acetate, which are the Z and E-(cis/trans) isomers (cis/trans) of each other. This ester has an unsaturated branched alkyl backbone to which an acetate group is attached. For this substance there are no experimental acute oral and dermal toxicity data 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 Neryl acetate multi the analogue approach is selected because for the main constituent, Neryl acetate mono acute oral and dermal toxicity information is available which can be used for read-across.

Hypothesis: Neryl acetate multi has the same acute oral and dermal toxicity as Neryl acetate mono.

Available information on acute oral: The oral acute toxicity of Neryl acetate mono was investigated in a study comparable to OECD TG 401 (non-GLP). In this study, 5 male and 5 female rats were administered a single oral dose of 5 mL (4555 mg/kg bw based on a relative density of 0.911) by gavage followed by a 14-day observation period. No mortality or other signs of toxicity were observed throughout the test. No clinical signs were noted. Based on these findings, the acute oral LD50 of Neryl acetate mono was determined to be >4555 mg/kg bw.

Available information on acute dermal: The dermal acute toxicity of Neryl acetate mono was investigated in a study comparable to OECD TG 402 (non-GLP). In this study, three groups of 4 rabbits were administered dermal doses of 2, 3.9, or 6.0 mL (1822, 3553, and 5466 mg/kg bw based on a relative density of 0.911) for 24 hours on intact and abraded skin, followed by a 14-day observation period. Treated skin was covered with a rubber sleeve or dam (occlusive exposure). Examination of treated skin after 24 hours, showed no signs of erythema or oedema, and remained normal during the 14-day observation period. No test item-related effects on feeding, body weight or behaviour were recorded. Haematology and urinalysis revealed no significant changes. No mortalities occurred. Based on these findings, the acute dermal LD50 of Neryl Acetate mono was determined to >5466 mg/kg bw.

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 toxicity.

Purity / Impurities

Neryl acetate multi is a multi-constituent. The other component is the E-isomer Geranyl acetate; together these have a purity of > 80%. There is one known impurity, which is << 10% and is similar to Neryl acetate.

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 Neryl acetate multi the substance Neryl acetate monowas selected because it is its key main constituent for which acute oral and dermal toxicity is available. 

Structural similarities and differences: Neryl acetate multi contains more than 50% Neryl acetate mono and thus being very representative for the multi. The other minor constituent is Geranyl acetate, which only difference is that it is the E-isomer of Neryl acetate.

Toxico-kinetics: Absorption vial all routes will be the same for Neryl acetate multi, its key constituent Neryl acetate and its E-isomer Geranyl acetate. Also metabolism will not be different between the Z and E-isomers.

Toxico-dynamics: The reactive site will be the same for Neryl acetate multi, its major constituent Neryl acetate mono and its E-isomer Geranyl acetate. The conjugated double bond-acetate group is the functional group and is the same for both constituents.

Uncertainty of the prediction: According to the ECHA dissemination site there is a study for Geranyl acetate resulting in an oral LD50 of 6330 mg/kg bw, which is in the same order of magnitude as derived for Neryl acetate multi. There are no remaining uncertainties other than those already addressed above.

ECHA site:https://echa.europa.eu/nl/registration-dossier/-/registered-dossier/19723/7/3/2/?documentUUID=895ce950-6f8b-4fbc-b416-076c07e26222

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 hazard and risk assessment

For Neryl acetate multi no acute oral and dermal toxicity is available. Neryl acetate mono being its key constituent is used for read across to fill this data gap. When using read across the result derived should be applicable for C&L and/or risk assessment. For the main component Neryl acetate mono, reliable acute oral and dermal toxicity data is available with an oral and dermal LD50 values of >4555 and >5466 mg/kg bw, respectively. These data can be used for read-across to Neryl acetate multi.

Final conclusion: For Neryl Acetate Multi the acute oral and dermalLD50 values are >4555 mg/kg bw and >5466 mg/kg bw are derived.

 

Data matrix supporting the read across to Neryl acetate multi from Neryl acetate mono for acute toxicity

Common name	Neryl acetate multi (Z and E-isomer or cis and trans)	Neryl acetate mono (Z-isomer, cis)	Geranyl acetate (E-isomer, trans)
	Target	Source Major constituent	Target Minor constituent
Systematic name	Multi-constituent	(2Z)-3,7-dimethylocta-2,6-dien-1-yl acetate	(2E)-3,7-dimethylocta-2,6-dien-1-yl acetate
Chemical structure	See constituents
% in product	>80%	55-65	ca. 40
CAS#	16409-44-2	141-12-8	105-87-3
EC#	240-458-0	205-459-2	203-341-5
Empirical formula	C12H20O2	C12H20O2	C12H20O2
Reach registration	Registered	Registered	Registered
Phys-chem *
MW	Not applicable	196	196
Appearance	Liquid	Liquid	Liquid
Vp (Pa)	2.12(exp.)	6.2(est.)	6.2(est.)
Ws (mg/L)	28.8(exp.)	18.2(est.)	18.2(est.)
log Kow	4.6 (exp.)	4.5(est.)	4.5(est.)
Human health
Acute oral LD50 mg/kg bw	>4555 (Read across)	>4555 (similar to OECD TG 401))	>4555 (Read across) 6330 (ECHA dissemination site)
Acute dermal LD50 mg/kg bw	> 5466 mg/kg bw (Read across)	>5466 mg/kg bw (similar to OECD TG 402)	>5466 mg/kg bw (Read across)

* Physico-chemical properties are calculated with EpiSuite unless stated otherwise i.e. ‘(exp.)’

 

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).