Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
in vitro stability in rat plasma
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 November 2014 to 22 April 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Objective of study:
other: calculation of half-life in plasma
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
A colormetric method was used to measure the time taken for the boric acid degradation product to neutralise one half of the sodium hydroxide molar equivalent.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Appearance/physical state: Clear colourless liquid
- Storage conditions: Room temperature in the dark

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
2-propyl-1-heptanol
boric acid

Any other information on results incl. tables

ANALYSIS OF ALCOHOL DEGRADATION PRODUCT BY GCMS

- The responses of the hydrolysis product (2-propyl-1-heptanol) in Experiment 1 are shown in Table 1 (attached).

- The results of Experiment 2 are shown in Table 2 (attached).

ANALYSIS OF BORIC ACID NEUTRALISATION OF SODIUM HYDROXIDE

- The results of Experiments 1 and 2 are shown in Table 3 (below).

TABLE 3 – TIME TAKEN FOR BORIC ACID NEUTRALISATION

Nominal concentration (mM)

Nomination concentration sodium hydroxide (mM)

Experiment 1 (seconds)

Experiment 2 (seconds)

Mean half-life (seconds)

0.6

0.3

65

67

66

Applicant's summary and conclusion

Conclusions:
The mean half-life of the test item hydrolysis was 66 seconds. No definitive data was obtained that enabled half-life data to be measured for the alcohol degradation product by GCMS, however, based on the data obtained it can be positively concluded that some hydrolysis has occurred almost immediately and potentially reaches a hydrolysis maximum within approximately 1 hour.
Executive summary:

METHODS

The purpose of the study was to develop methods that would enable the in vitro stability of the test item in rat plasma to be measured and where possible calculate a half-life value for the test item. The test item was known to rapidly degrade in water to boric acid and 2-propyl-1-heptanol. Two approaches were taken, analysis of the formation of the alcohol degradation product by GCMS and a colormetric indicator method. This measured the time taken for one half the amount of sodium hydroxide molar equivalent necessary to neutralize the boric acid resulting from complete hydrolysis of the ester.

 

RESULTS

The mean half-life of the test item hydrolysis was determined to be 66 seconds. No definitive data was obtained that enabled half-life data to be measured for the alcohol degradation product by GCMS, however, based on the data obtained it can be positively concluded that some hydrolysis has occurred almost immediately and potentially reaches a hydrolysis maximum within approximately 1 hour.