D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1)

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

Because the test substance forms sparingly soluble precipitates with the buffer ions recommended in the Guideline, test was run in aqueous solutions. The pH was adjusted using gluconic acid or NaOH.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Version / remarks:

cited as 92/69/EEC C.07

Deviations:

yes

Remarks:

Because the test substance forms sparingly soluble precipitates with the buffer ions recommended in the Guideline, test was run in aqueous solutions. The pH was adjusted using gluconic acid or NaOH.

Principles of method if other than guideline:

Only preliminary test performed

GLP compliance:

yes (incl. QA statement)

Remarks:

Degussa AG, Zentrale Forschungseinrichtungen Chromatographie und Organische Analytik

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: At each day (1, 2, 3, 4, and 5 d) sample solutions together with calibration solutions (Chlorhexidine and p-Chloroaniline) were measured.

Details on test conditions:

TEST SYSTEM
- Details of traps for volatile, if any: Chlorhexidine is not volatile from aqueous solutions
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no

TEST MEDIUM
- Preparation of test medium: Ca. 5.0 g test substance (Chlorhexidine gluconate solution 20%) were transferred into 100 mL volumetric flask, 90 mL water were added, target pH was adjusted using gluconic acid (prepared as a 10% solution of glucono-d-lactone) or 0.1 M sodium hydroxyde solution to pH 4.0, 7.0, and 9.0, and the flasks were filled to the volume with water.
- Test concentrations: ca. 10 g/L
- Temperature: 50°C
- Identity and concentration of co-solvent: No co-solvent was used

OTHER TEST CONDITIONS
- Adjustment of pH: After each day, pH of the 3 test solutions were corrected if necessary. The changes in volume by adding small quantities of dilute solutions of gluconic acid or sodium hydroxyde were below 1% of the total volume

Duration:

5 d

pH:

4

Duration:

5 d

pH:

7

Duration:

5 d

pH:

9

Number of replicates:

1

Positive controls:

no

Remarks:

Reference substance not required by the Guideline

Preliminary study:

In the preliminary test, no significant hydrolysis was observed at all pH values. Changes in concentrations were below 10%.

Transformation products:

yes

No.:

#1

% Recovery:

> 90

Temp.:

50 °C

Duration:

5 d

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

Degradation: < 10% after 5 days at pH 4, 7 and 9 (50°C)

Analytical results for the preliminary test of Chlorhexidine (CHD), p‑Chloroaniline (PCA) and unknown inpurities (calculated as CHD):

pH 4.0:

Time	start	day 1	day 2	day 3	day 4	day 5
CHD [%]	0.50	0.53	0.54	0.52	0.58	0.54
PCA [%]	n.d.	0.0003	0.0002	0.0004	0.0004	0.0005
Impurities [mg/kg]	75	85	81	102	106	99

 

pH 7.0:

Time	start	day 1	day 2	day 3	day 4	day 5
CHD [%]	0.55	0.54	0.52	0.53	0.54	0.52
PCA [%]	0.0002	n.d.	n.d.	0.0002	0.0002	0.0003
Impurities [mg/kg]	85	88	89	78	90	86

 

pH 9.0:

Time	start	day 1	day 2	day 3	day 4	day 5
CHD [%]	0.56	0.53	0.55	0.53	0.54	0.53
PCA [%]	0.0001	0.0002	0.0001	0.0003	0.0003	0.0003
Impurities [mg/kg]	82	89	110	118	131	138

 

The results reveal that the concentration of Chlorhexidine remains constant at all pH values over the test period of 5 days. The concentrations do not change by more than 10% during the test period. The preliminary test was sufficient.

In the HPLC column, separation of the base Chlorhexidine and Gluconate is expected. As only Chlorhexidine base was detected, the test reveals that the base is not hydrolyzable. Due to the molecular structure, hydrolysis of gluconic acid is not expected.

Validity criteria fulfilled:

yes

Conclusions:

It can be concluded that under environmental conditions the hydrolysis half-life time of Chlorhexidine base is more than 1 year.

Description of key information

Under environmental conditions the hydrolysis half-life of Chlorhexidine base is more than 1 year. 

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

20 °C

Additional information

Hydrolysis of Chlorhexidine digluconate has been performed according to OECD Guideline 111 and EEC-Guideline C.07. No significant hydrolysis was observed at all pH values.