1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidised

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

February, March 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

This study was not performed according to international guideline and is not GLP as this is a standard company internal data conducted for global knowledge. This study is well documented and is considered reliable with restrictions.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The aim of the study is to assess the stability of the substance in a series of simple media simulating perfumery applications. The test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1 % of non ionic surfactant. The tests are done in accelerated conditions at 40°C during ca. one month.

GLP compliance:

no

Remarks:

Standard company internal data measurements conducted for global knowledge.

Specific details on test material used for the study:

No additional information

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

200 – 300 ppm of raw material are dissolved in the pH buffer containing the surfactant (Arkopal N 150) and put into storage in an oven at 40°C. Small aliquots of the test solution are extracted with an organic solvent (typically cyclohexane or ethyl acetate) containing a hydrocarbon standard (typically C12, C17 or C20) on a regular basis throughout the test (typically at time = 0, 0.25, 1, 2, 4, 7, 15, 21 and 28 days). The extracts are analyzed by GC-FID and the results are plotted as (Area/Area Std) expressed in [%]. The measurement at time = 0 is set at 100% and the succeeding measurements are calculated relatively to the time = 0 measurement. Therefore the curves represent the percentage of product remaining in the test solution at the time of analysis.

Buffers:

Buffer solutions:
pH 2 (± 0.1) buffer: Reference Handbook of Chemistry and Physics buffer type A
pH 5 (± 0.1) buffer: Reference Handbook of Chemistry and Physics buffer type C
pH 7 (± 0.1) buffer: Reference Handbook of Chemistry and Physics buffer type D
pH 8.5 (± 0.1) buffer: Reference Handbook of Chemistry and Physics buffer type F
pH 12 (± 0.1) buffer: Reference Handbook of Chemistry and Physics buffer type I

Estimation method (if used):

Not applicable

Details on test conditions:

No data

Duration:

28 d

pH:

2

Temp.:

40 °C

Initial conc. measured:

> 200 - < 300 other: ppm

Duration:

28 d

pH:

5

Temp.:

40 °C

Initial conc. measured:

> 200 - < 300 other: ppm

Duration:

28 d

pH:

7

Temp.:

40 °C

Initial conc. measured:

> 200 - < 300 other: ppm

Duration:

28 d

pH:

8.5

Temp.:

40 °C

Initial conc. measured:

> 200 - < 300 other: ppm

Duration:

28 d

pH:

12

Temp.:

40 °C

Initial conc. measured:

> 200 - < 300 other: ppm

Number of replicates:

1 for each pH.

Positive controls:

no

Negative controls:

no

Statistical methods:

None

Preliminary study:

None

Test performance:

No data

Transformation products:

no

Details on hydrolysis and appearance of transformation product(s):

Results showed that the disappearance of the parent compound after 5 days is less than 10% at any pH (from 5 to 12) at 40 °C. It can be concluded that under the conditions of the present test and at pH from 5 to 12, test substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH). Under very acidic conditions pH (pH 2), the test substance hydrolyses very rapidly and disappears up to 100% in the first minutes. After 28 days, at pH 5, the test substance disappeared up to 50% but was stable at environmentally relevant pH (7 and 8.5) at 40°C and also under very basic conditions (pH 12).

% Recovery:

ca. 0

pH:

2

Temp.:

40 °C

Duration:

ca. 5 d

Remarks on result:

other: The test substance hydrolyses very rapidly and disappears up to 100% in the first minutes.

% Recovery:

> 90

pH:

5

Temp.:

40 °C

Duration:

5 d

% Recovery:

ca. 50

pH:

5

Temp.:

40 °C

Duration:

28 d

% Recovery:

> 90

pH:

7

Temp.:

40 °C

Duration:

ca. 5 - ca. 28 d

% Recovery:

> 90

pH:

8.5

Temp.:

40 °C

Duration:

ca. 5 - ca. 28 d

% Recovery:

> 90

pH:

12

Temp.:

40 °C

Duration:

ca. 5 - ca. 28 d

Remarks on result:

not measured/tested

Other kinetic parameters:

None

Details on results:

No additional information

None

Validity criteria fulfilled:

yes

Conclusions:

The disappearance of the parent compound after 5 days is less than 10% at any pH (from 5 to 12) at 40 °C. It can be concluded that under the conditions of the present test and at pH from 5 to 12, test substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH). Under very acidic conditions pH (pH 2), the test substance hydrolyses very rapidly and disappears up to 100% in the first minutes. After 28 days, at pH 5, the test substance disappeared up to 50% but was stable at environmentally relevant pH (7 and 8.5) at 40°C and also under very basic conditions (pH 12).

Executive summary:

This hydrolysis study was not performed according to international guideline and is not GLP as this is a standard company internal data conducted for global knowledge. The aim of the study is to assess the stability of the substance in a series of simple media simulating perfumery applications. The test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1% of non ionic surfactant (Arkopal N 150). The tests are done in accelerated conditions at 40 °C during ca. one month.

200 – 300 ppm of raw material are dissolved in the pH buffer containing the surfactant (Arkopal N 150) and put into storage in an oven at 40°C. Small aliquots of the test solution are extracted with an organic solvent (typically cyclohexane or ethyl acetate) containing a hydrocarbon standard (typically C12, C17 or C20) on a regular basis throughout the test (typically at time = 0, 0.25, 1, 2, 4, 7, 15, 21 and 28 days). The extracts are analyzed by GC-FID and the results are plotted as (Area/Area Std) expressed in [%]. The measurement at time = 0 is set at 100% and the succeeding measurements are calculated relatively to the time = 0 measurement. Therefore the curves represent the percentage of product remaining in the test solution at the time of analysis.

 

The disappearance of the parent compound after 5 days is less than 10% at any pH (from 5 to 12) at 40 °C. It can be concluded that under the conditions of the present test and at pH from 5 to 12, test substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH). Under very acidic conditions pH (pH 2), the test substance hydrolyses very rapidly and disappears up to 100% in the first minutes. After 28 days, at pH 5, the test substance disappeared up to 50% but was stable at environmentally relevant pH (7 and 8.5) at 40°C and also under very basic conditions (pH 12).

Description of key information

Weight of evidence approach:

The registered substance is hydrolytically stable at pH from 5 to 12 but unstable at pH lower than 5.

The registered substance is a macrocyclic compound containing three potentially acid sensitive functionalities:

- The epoxide function of a trisubtituted double bond: in acidic conditions and already at pH 5, the epoxide could open up generating an alcohol and a tertiary carbocation (stabilized intermediate) which could then be intercepted by water to form an alcohol. Globally the epoxide has been transformed to a diol.

- The two trisubstituted double bonds in the molecule: in acidic media an hydration reaction could take place and would lead to tertiary alcohol.

Therefore, the registered substance in acidic media will hydrolyze to give poly-hydroxylated product.

Additional information

To assess the hydrolysis potential of the registered substance, a stability test and an expert statement was provided in the dossier.

The stability study was not performed according to international guideline and is not GLP as this is a standard company internal data conducted for global knowledge. The aim of the study is to assess the stability of the substance in a series of simple media simulating perfumery applications. The test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1% of non ionic surfactant (Arkopal N 150). The tests are done in accelerated conditions at 40 °C during ca. one month. According to this study, the disappearance of the parent compound after 5 days is less than 10% at any pH (from 5 to 12) at 40°

C. It can be concluded that under the conditions of the present test and at pH from 5 to 12, the registered substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH). Under very acidic conditions pH (pH 2), the substance hydrolyses very rapidly and disappears up to 100% in the first minutes. After 28 days, at pH 5, the substance disappeared up to 50% but was stable at environmentally relevant pH (7 and 8.5) at 40°C and also under very basic conditions (pH 12).

 

Furthermore, according to an expert statement, the registered substance is a macrocyclic compound containing three potentially acid sensitive functionalities. The first one is an epoxide of a trisubstituted double bond. In acidic conditions and already at pH 5 this could open up generating an alcohol and a tertiary carbocation (stabilized intermediate) which could then be intercepted by water to form an alcohol. Globally the epoxide has been transformed to a diol. The second one is trisubstituted double bonds (two in this molecule). In acidic media an hydration reaction could take place and would lead to tertiary alcohol. From neutral to basic conditions epoxide and double bond are not likely to hydrolyze under such soft reaction conditions. As a conclusion, the registered substance in acidic media will hydrolyze to give poly-hydroxylated product (see attached picture).