3-iodo-2-propynyl butylcarbamate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1986-02 to 1986-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA Guideline Subdivision N 161-1 (Hydrolysis)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL RADIOLABELLED
- Source and lot/batch No.of test material: CFQ 4316, Amersham International plc

Radiolabelling:

yes

Analytical monitoring:

yes

Buffers:

- pH: 5, 7, 9

Details on test conditions:

TEST SYSTEM
The preparation of saturated buffered solutions of the test item, and their incubation at 25 °C were described in the 'Procedures' section of Report No. 4166 (IRI Project No. 135124).

Duration:

1 mo

pH:

5

Temp.:

25 °C

Remarks:

saturated solution

Duration:

1 mo

pH:

7

Temp.:

25 °C

Remarks:

saturated solution

Duration:

1 mo

pH:

9

Temp.:

25 °C

Remarks:

saturated solution

Positive controls:

no

Negative controls:

no

Transformation products:

yes

Remarks:

transformation products not completely identified

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

- Transformation products:
Product 1: Longer retention time than test item upon radio-HPLC analysis; strongly UV absorbance (239 nm)
Product 2: Shorter retention time than test item upon radio-HPLC analysis; no significant UV absorbance

Details on results:

MAJOR TRANSFORMATION PRODUCTS

- At pH9:
Radio-HPLC analysis of samples together with blank buffered solutions showed that degradation of the test item was occurring significantly only in the pH 9.0 buffer

Results with reference substance:

not applicable

Validity criteria fulfilled:

not specified

Conclusions:

Two major degradation products were detected at pH 9.

Executive summary:

1. Degradation of the test item was observed when saturated solutions of [14C]-labeled test item buffered at pH 9.0 were incubated at 25 °C over the period of a month. No degradation products were detected when saturated solutions of [14C]-labeled test item buffered at pH 5.0 and 7.0 were similarly treated.

2. Two major degradation products were detected in pH 9.0 buffer by reverse phase radio-HPLC analysis:
Product 1 had no significant absorbance in the UV region and a retention time less than the test item. Product 2 had high UV absorbance and a longer retention time than the test item.

3. Degradation of with sodium hydroxide produced products with chromatographic and absorbance properties very similar to those observed when the test item was incubated in pH 9.0 buffer.

4. The non-UV absorbing alkaline hydrolysis product of the test item was stable under alkaline conditions and co-chromatographed with n-butylamine in HPLC using refractive index detection. GC/MS with selected ion monitoring provided additional evidence that this product was n-butylamine ("Product 1").

5. The high UV absorbance alkaline hydrolysis product of the test item ("Product 2") further degraded under both alkaline and acid conditions, with no loss of radioactivity. Tentative evidence that Product 1 (n-butylamine) could be produced by acid treatment of Product 2 was provided by radio-HPLC.

6. A heptafluorobutyryl derivative of the test item was identified by GC/MS, but no other derivatives of the alkaline degradation products were detected after this form of derivatisation.

7. Trimethylsilyl (TMS)-derivatives of alkaline degradation products of the test item were detected by GC/MS following derivatisation with BSTFA. The molecular weight and fragmentation pattern of one component suggested the presence of an hydrolysis product which was a TMS derivative of the IPBC molecule but containing no Iodine atom.

Further work is necessary to confirm this identification and to investigate the nature of the high UV absorbance component ("Product 2").

Description of key information

The test item was very rapidly degraded in pH 9 buffered solution, slowly degraded in pH 7 buffered solution, and determined to be hydrolytically stable in pH 5 buffered solution.

In a supportive study two major degradation products were detected at pH 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

139 d

at the temperature of:

25 °C

Additional information

Key study

Test item was very rapidly degraded in pH 9 buffered solution, slowly degraded in pH 7 buffered solution (half-life = 139 days, at a temperature of 25 °C), and determined to be hydrolytically stable in pH 5 buffered solution. The only metabolite detected from pH 9 and 7 samples was propargyl butyl carbamate.

Supporting investigation of hydrolysis products

1. Degradation of the test item was observed when saturated solutions of [14C]-labeled test item buffered at pH 9.0 were incubated at 25 °C over the period of a month. No degradation products were detected when saturated solutions of [14C]-labeled test item buffered at pH 5.0 and 7.0 were similarly treated.

2. Two major degradation products were detected in pH 9.0 buffer by reverse phase radio-HPLC analysis:
Product 1 had no significant absorbance in the UV region and a retention time less than the test item. Product 2 had high UV absorbance and a longer retention time than the test item.

3. Degradation of with sodium hydroxide produced products with chromatographic and absorbance properties very similar to those observed when the test item was incubated in pH 9.0 buffer.

4. The non-UV absorbing alkaline hydrolysis product of the test item was stable under alkaline conditions and co-chromatographed with n-butylamine in HPLC using refractive index detection. GC/MS with selected ion monitoring provided additional evidence that this product was n-butylamine ("Product 1").

5. The high UV absorbance alkaline hydrolysis product of the test item ("Product 2") further degraded under both alkaline and acid conditions, with no loss of radioactivity. Tentative evidence that Product 1 (n-butylamine) could be produced by acid treatment of Product 2 was provided by radio-HPLC.

6. A heptafluorobutyryl derivative of the test item was identified by GC/MS, but no other derivatives of the alkaline degradation products were detected after this form of derivatisation.

7. Trimethylsilyl (TMS)-derivatives of alkaline degradation products of the test item were detected by GC/MS following derivatisation with BSTFA. The molecular weight and fragmentation pattern of one component suggested the presence of an hydrolysis product which was a TMS derivative of the IPBC molecule but containing no Iodine atom.