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Administrative data

Description of key information

Acute oral toxicity: 6300 mg/kg bw based on read across from Myrcenyl acetate which was tested in OECD TG 401.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across information.
Justification for type of information:
The read across rationale is presented in the related Endpoint summary, the accompanying files are also attached there.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
6 300 mg/kg bw
Based on:
test mat.
95% CL:
>= 5 300 - <= 7 300
Interpretation of results:
other: Not acute harmful
Remarks:
According to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
The LD50 value for the substance is >5000 mg/kg bw, based on read across from Myrcenyl Acete.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been follo wed but not GLP.
Justification for type of information:
The information is used for read across to Pseudo linalyl acetate.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
Test was done before GLP came into force.
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 250 gram
- Fasting period before study: a minimum of 16 hours prior to administration of the test material
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: unspecified
Details on oral exposure:
Test substance was administered as a concentrate.
Doses:
4000, 5000, 6250 and 7800 mg/kg bw
No. of animals per sex per dose:
10 per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations: Observations for mortality were made at 1 and 6 hours after application and thereafter daily.
- Necropsy of survivors performed: Gross necropsies were performed on all survivors.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
6 300 mg/kg bw
Based on:
test mat.
95% CL:
>= 5 300 - <= 7 300
Mortality:
Dose: Deaths
4000 mg/kg bw: 1/10
5000 mg/kg bw: 3/10
6250 mg/kg bw: 5/10
7800 mg/kg bw: 7/10
Deaths occurred overnight to three days following administration of the drug.
Clinical signs:
The rats experienced piloerection and lethargy.
Interpretation of results:
other: Not acute harmful
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
The acute oral toxicity test showed a calculated LD50 of 6300 mg/kg bw.
Executive summary:

Acute oral toxicity: In this study, 40 male rats (10/dose) were administered the substance at dose levels of 4000, 5000, 6250, 7800 mg/kg bw. The test material was administered as a concentrate. At dosage 4000 mg/kg bw 1/10 animals died, at 5000 mg/kg bw 3/10 animals died, at 6250 mg/kg bw 5/10 animals died and at 7800 mg/kg bw 7/10 animals died. The rats experienced piloerection and lethargy. Deaths occurred overnight to three days following administration of the substance. The calculated acute oral LD50 is 6300 mg/kg bw, the 95% confidence limit is 5300-7300 mg/kg bw.

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.

Additional information

Acute oral toxicity is assessed based on read-across to Pseudo linalyl acetate from Myrcenyl acetate 'mono'. The executive summary of the source information is presented below, followed by the read-across rationale.

Myrcenyl acetate 'mono' acute oral toxicity test information

In a study equivalent to OECD TG 401, 40 male rats (10/dose) were administered the substance at dose levels of 4000, 5000, 6250, 7800 mg/kg bw. The test material was administered as a concentrate. At dosage 4000 mg/kg bw 1/10 animals died, at 5000 mg/kg bw 3/10 animals died, at 6250 mg/kg bw 5/10 animals died and at 7800 mg/kg bw 7/10 animals died. The rats experienced piloerection and lethargy. Deaths occurred overnight to three days following administration of the substance. The calculated acute oral LD50 is 6300 mg/kg bw, the 95% confidence limit is 5300-7300 mg/kg bw.

The acute oral toxicity of Pseudo linalyl acetate using read across from Myrcenyl acetate ‘mono’ (CAS 1118-39-4)

 

Introduction and hypothesis for the analogue approach

Pseudo linalyl acetate has one major, two minor constituents and a number of impurities. Myrcenyl acetate ‘mono’ with 25-35% is the main constituent. Alpha and Gamma Terpinlyl acetate are the minor ones, each between 10-20%. For Pseudo linalyl acetate no acute oral toxicity information is 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 toxicity of Pseudo linalyl acetate the analogue approach is selected because for its major constituents Myrcenyl acetate ‘mono’ acute oral toxicity information is available which can be used for read across.

Hypothesis: Pseudo linalyl acetate’s acute oral toxicity can be predicted with the acute LD50 of Myrcenyl acetate ‘mono’, being its major key constituent, which can cover the substance as a whole.

Available information: For Myrcenyl acetate ‘mono’ an acute oral toxicity study was performed, in which 40 male rats (10/dose) were exposed to doses of 4000, 5000, 6250 or 7800 mg/kg bw (concentrated test item). The rats were observed for 14 days following exposure. At 4000 mg/kg bw, 1/10 animals died, at 5000 mg/kg bw 3/10 animals died, at 6250 mg/kg bw 5/10 animals died and at 7800 mg/kg bw 7/10 animals died. The exposed rats showed piloerection and lethargy. Deaths occurred overnight to three days following administration of the test item. The calculated oral LD50 was 6300 mg/ kg bw with a 95% confidence limit of 5300 – 7300 mg/kg bw.

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical(s) are shown in the data matrix, including physico-chemical properties and available toxicologicalinformation.

Purity / Impurities

Pseudo linalyl acetate’s key constituents are covered by Myrcenyl acetate ‘mono’. All impurities (< 10%) are not expected to impact the assessment. In Appendix 1 all components are presented.

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: The key constituent of Pseudo linalyl acetate is selected as an analogue, which is Myrcenyl acetate ‘mono’ for which acute oral toxicity information is available. Supporting information is available from Alpha-Terpinyl acetate.

Structural similarities and differences: All constituents of Pseudo linalyl acetate and thus including Myrcenyl acetate ‘mono’ have a hydrocarbon backbone with one or more (non-)conjugated double bonds. The hydrocarbon backbone is mostly a chain but can be cyclic as well. The constituents have an acetate ester attached to of the chain. The difference is that the major constituent has a straight alkyl chain, while the minor ones are cyclic. Some impurities are alcohol derivative of the acetates. These minor differences are not expected to affect the LD50. 

Toxico-kinetics, oral absorption: Pseudo linalyl acetate’s constituents and thus including Myrcenyl acetate ‘mono’ have molecular weight and log Kow favourable for oral uptake and full oral absorption is expected.Metabolism: The Pseudo linalyl acetate acetic esters constituents will be metabolised by carboxyl esterases in the gut and/or liver (Toxicological handbooks) in their respective secondary and tertiary alcohols (EFSA, 2011 on tertiary alcohols and esters). The terminal methyl groups can be oxidized into more water soluble primary alcohol metabolites. These pathways are applicable to the constituents of Pseudo linalyl acetate and its impurities.

Toxico-dynamics: Myrcenyl acetate ‘mono’ is expected to be similarly reactive as the other constituents based on the similar LD50’s of Myrcenyl acetate ‘mono’ and Alpha-Terpinyl acetate and these will cover the other constituent (Gamma-Terpinyl acetate) and impurities as well based on the structural similarity.

Uncertainty of the prediction: There are no other remaining uncertainties than those which are already discussed above.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the data matrix below.

Conclusions per endpoint for hazard and risk assessment

For Pseudo linalyl acetate no acute oral toxicity information was available. For its key constituent Myrcenyl acetate ‘mono’ acute oral toxicity was available which can be used for read across. 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, which is presented in the current document.For Myrcenyl acetate ‘mono’ an acute oral toxicity test is available (Reliability 2) with an LD50 of 6300 mg/kg bw which can be read-across to Pseudo linalyl acetate.

Final conclusion: Pseudo linalyl acetate has an LD50 of 6300 mg/kg bw.

 

Data matrix for the read across to Pseudo linalyl acetate from Myrcenyl acetate ‘mono’ for acute oral toxicity

Common name

Pseudo linalyl acetate

Myrcenyl acetate ‘mono’

Alpha-Terpinyl acetate

Gamma-Terpinyl acetate

 

Target

Source (Major constituent)

Source supporting (Minor constituent)

Minor constituent

Structure

Reaction mass

 

CAS #

--

1118-39-4

80-26-2

10235-63-9

EC #

944-488-1

214-262-0

201-265-7

233-564-3

REACH registration

2018

2018

Registered

Not found

Empirical formula

Not available

C12H20O2

C12H20O2

C12H20O2

Molecular weight

Not available

196.29

196.29

196.29

Physico-chemical

 

 

EpiSuite

EpiSuite

Log Kow

4.4 (exp.)

4.4 (exp.)

4.3

4.5

Human health endpoints

 

 

 

 

Acute oral

 

6300mg/kg bw

(Read-across)

6300mg/kg bw

(OECD TG 401)

5075 mg/kg bw

 (OECD TG 401)

6300mg/kg bw

(Read-across)

 

Reference

- EFSA, 2011 Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF), European Food Safety Authority (EFSA), Scientific Opinion on Flavouring Group Evaluation 18, Revision 2: Aliphatic, alicyclic and aromatic saturated and unsaturated tertiary alcohols, aromatic tertiary alcohols and their esters from chemical groups 6 and 8, site visited, April 2018,https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2011.1847

 

Appendix 1: Constituents and possible impurities of Pseudo linalyl acetate

CAS#

Type of constituent

Type and Name

 

 

Esters linear and alicyclic

1118-39-4

Major

2-methyl-6-methylideneoct-7-en-2-yl acetate (Myrcenyl acetate ‘mono’)

7643-61-0

Impurity

(5Z)-2,6-dimethylocta-5,7-dien-2-yl acetate

7643-62-1

Impurity

(5Z)-2,6-dimethylocta-5,7-dien-2-yl acetate

105-87-3 *

Impurity

(2E)-3,7-dimethylocta-2,6-dien-1-yl acetate (Geranyl acetate)

80-26-2 *

Minor

2-(4-methylcyclohex-3-en-1-yl)propan-2-yl acetate (Alpha-Terpinyl acetate)

150461-96-4

Impurity

1-(3,3-dimethylcyclohex-1-en-1-yl)ethyl acetate

150461-97-5

Impurity

1-(5,5-dimethylcyclohex-1-en-1-yl)ethyl acetate

10235-63-9

Minor

1-methyl-4-(propan-2-ylidene) cyclohexyl acetate (Gamma-Terpinyl acetate)

20777-47-3

Impurity

cis-1-methyl-4-(prop-1-en-2-yl)cyclohexyl acetate (Beta-terpinyl acetate)

97890-05-6

Impurity

(2Z)-2-(3,3-dimethylcyclohexylidene)ethyl acetate

76-49-3

Impurity

(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylrel-acetate (Bornyl acetate)

210648-12-7

Impurity

3,3,5-trimethylcyclohept-4-en-1-yl acetate

 

 

Alcohol linear and alicyclic

543-39-5

Impurity

2-methyl-6-methylideneoct-7-en-2-ol (Myrcenol)

98-55-5 *

Impurity

2-(4-methylcyclohex-3-en-1-yl)propan-2-ol (Alpha-Terpineol)

586-81-2

Impurity

1-methyl-4-(propan-2-ylidene)cyclohexanol (Gamma-terpineol)

 

Justification for classification or non-classification

Based on the results, the substance does not need to be classified for acute oral toxicity according to EU CLP (EC No. 1272/2008 and its amendments).