Isophthaloyl dichloride

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

Temperature used was 0°C.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Isophthaloyl dichloride

EC Number:

202-774-7

EC Name:

Isophthaloyl dichloride

Cas Number:

99-63-8

Molecular formula:

C8H4Cl2O2

IUPAC Name:

benzene-1,3-dicarbonyl dichloride

Details on test material:

- Purity: > 99%

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

1. Reaction rate constant and half-life at pH 4, 7 and 9 (0°C) with 2 replicates each.
2. Concentrations of test substance at pH 4, 7 and 9 (0°C) with 2 replicates each between 11 and 13 evenly spaced time intervals for up to 3600 seconds.
3. Formation of the acid (final product) and half-acid at pH 4, 7 and 10 (0°C) with 1 replicate each at approx. 12 evenly spaced time intervals for up to 6000 seconds.
4. Formation of the acid (final product) and half-acid at pH 7 and 25°C with 1 replicate at 11 approx. evenly spaced time intervals for up to 1200 seconds.

Buffers:

The pH buffer compositions were slightly different for the two study measurements. Capacity of the buffers was checked by measuring the pH of the buffers after the acid chloride was added. All buffers showed no significant change in pH. The temperature of the water bath used to maintain the test solutions at a constant temperature did not fluctuate significantly at 0 and 25°C.

All buffer solutions were made with water.

EXPERIMENT SERIES 1: MEASUREMENT of the HYDROLYSIS RATE
pH 4: 500 mL of 0.100 M potassium hydrogen phthalate [KH (CHO844)] and 4.00 mL of 0.100 N sodium hydroxide (NaOH) diluted to 1.000 L with water. No final pH adjustment was necessary.
pH 7: 500 mL of 0.100 M potassium dihydrogen phosphate (KHPO24) and 296 mL of 0.100 M sodium hydroxide diluted to 1.000 L with water.
pH 9: 500 mL 0.050 M boric acid (HBO22) and 213 mL of 0.100 M NaOH diluted to 1.000 L with water. No final pH adjustment was necessary.

EXPERIMENT SERIES 2: FORMATION and IDENTIFICATION of HYDROLYSIS PRODUCTS
pH 4: Acetate buffer 0.05 M concentration contained 0.0426 M glacial acetic acid and 0.0074 M sodium acetate. No adjustments were made.
pH 7: Phosphate buffer 0.05M concentration contained 0.020 M potassium dihydrogen phosphate and 0.030 M sodium monohydrogen phosphate heptahydrate. No adjustments were made.
pH 10: Carbonate buffer 0.05M concentration contained 0.025 M sodium bicarbonate and 0.025 M sodium carbonate. No adjustments were made.

Estimation method (if used):

The concentration of the test substance was determined as a function of time. The logarithms of the concentrations between 20 and 70% hydrolysis of the test substance initially added to the test system were plotted against time. The slope of the resulting straight line (assuming first-order or pseudo-first order behaviour) gives the rate constant from the formula if log10 is used:
kobs = - slope x 2.303/t

The units of this constant kobs have the dimension of (time)-1. The half-life of the reaction (time for 50% of the substance to react, t½) is:
t = 0.693 / kobs

Details on test conditions:

- To stop the hydrolisation reaction at the desired intervals 40% aqueous dimethylamine is added. This leads to the quantitive formation of N,N,N,N-tetramethylterephthalamide (ICL-adduct). For time t = 0, 300 μL of DMA was added to one of the vials, which was shaken vigorously (this is the time 0 vial). A temperature probe was placed in the time 0 vial and all vials needed for the experiment were placed in the water bath at 0°C. The vials were allowed to equilibrate to the temperature of the water bath as indicated by the temperature in the time 0 vial. The temperature in the t = 0 vial was recorded before each vial was used. While keeping the vial in the water bath, the cap was removed and 250 μL of the ICl stock solution was added to the buffer solution. The vial was capped and shaken vigorously by holding the vial by the cap so as not to warm the test system. As soon as the vial was returned to the water bath, the timer was started. At the designated time interval, the cap was removed, 300 μL of DMA was added, the vial capped, the vial shaken vigorously, and the vial placed back into the water bath. The t = 0 vial that already contained 300 μL of DMA was then removed from the water bath and 250 μL of the ICl stock solution was added. The vial was then capped, shaken vigorously, and placed back in the water bath.
The purpose of DMA addition was two-fold: to quench the reaction by rapidly reacting with any remaining ICl and to provide a derivative that was amenable to analysis by gas chromatography. Preliminary experiments and method validation confirmed that addition of DMA to the test medium resulted in quantitative conversion of ICl to N,N,N’,N’-tetramethylterephthalamide (the “DMA-adduct”).
- Extraction (solvent used, method: e.g. liquid-liquid, SPE): While keeping the vials in the water bath, 5 mL of methylene chloride was added to each vial to extract the DMA-adduct from the test vial. Each vial was quickly capped and shaken vigorously by holding it by the cap so as not to warm the test solution in the vial. The vial was then placed back in the water bath and allowed to stand for a minimum of two minutes. The methylene chloride was removed from the vial using a glass pipette and placed into a separate 10 mL glass vial for analysis. The original 40 mL vial was placed back in the water bath. Extraction with 5 mL of methylene chloride was repeated twice more, making sure that all of the methylene chloride was visibly removed after each of the three extractions.

Details of the various other procedures are covered in the study reports.

Number of replicates:

See "Details on sampling"

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

Regression analysis performed with Microsoft® EXCEL 2000.

Results and discussion

Preliminary study:

The hydrolysis study was initially performed at pH 7 and 15°C. The concentration of ICL after 30 seconds had decreased by approximately 85%. This indicated that hydrolysis occurred quickly, and that samples would be difficult to collect at temperatures of 15°C and greater to provide a minimum of 6 spaced data points between 20 and 70% hydrolysis, as required by OECD guidelines.

Transformation products:

yes

Identity of transformation products

Identity of transformation products 1

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

Isophthalic acid (CAS 121-91-5)

Identifier:

other:

Identity:

Isophthalic acid (CAS 121-91-5)

Identity of transformation products 2

No.:

#2

Reference

Reference substance name:

Unnamed

IUPAC name:

Half-acid

Identifier:

other:

Identity:

Half-acid

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

A short-lived intermediate, in which one of the two carboxylic acid (designated as the half-acid), is formed. Half–acid concentration reached a maximum and began to decline within 3, 3, and 2 minutes of the start of the experiment at pH 4, 7, and 10, respectively, and 0ºC. Half-acid concentration reached a maximum began to decline within 30 seconds at pH 7 and 25°C. By the end of the studies, half-acid concentrations measured in water at pH 4, 7, and 10 at 0ºC and at pH 7 and 25°C were not detected (ND) in the aqueous solutions.

The half-acid undergoes additional hydrolysis, in which the remaining chloride functionality transforms to carboxylic acid to form isophthalic acid (IPA). The two chloride functionalities in ICL also may undergo simultaneous transformation to IPS. Formation of IPA reached 50% of maximum or higher within 4, 4, and 1 minutes at pH 4, 7, and 10 at 0ºC, and greater than 90% of the ICL initially added within 30 minutes. Formation of IPA reached 50% of the maximum or higher within 15 seconds at pH 7 and 25°C.

The determination of ICL, half-acid, and IPA resulted in a mass (material) balance greater than 95%.

The time in which 50% of the test substance will transform at environmentally relevant pH ranges and temperatures is less than 6 minutes (t1/2 < 6 minutes). The final product of ICL hydrolysis is IPA.

Total recovery of test substance (in %)

% Recovery:

> 90

pH:

7

Duration:

60 min

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

0 °C

Hydrolysis rate constant:

32 400 000 s-1

DT50:

3.9 min

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

0 °C

Hydrolysis rate constant:

24 100 000 s-1

DT50:

4.9 min

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

0 °C

Hydrolysis rate constant:

52 500 000 s-1

DT50:

2.2 min

Type:

(pseudo-)first order (= half-life)

Any other information on results incl. tables

Stability of the test substance, ICL

• ICL had an average half-life (t½) in water at 0°C of 3.86, 4.86 and 2.21 minutes at pH 4, 7 and 9, respectively.

• Observed first-order rate constants (kobs) at 0°C averaged 324, 241, and 525 (x 10⁵s^-1) at pH 4, 7 and 9, respectively.

 

Formation and reaction of the Half-acid

• Half-acid concentration reached a maximum and began to decline within 3, 3 and 2 minutes of the start of the experiment at pH 4, 7 and 10, respectively, at 0°C.

• Half-acid concentration reached a maximum and began to decline within 30 seconds at pH 7 and 25°C.

• By the end of the studies, Half-acid concentrations measured in water at pH 4, 7 and 10 at 0°C and at pH 7 and 25°C were not detected in the aqueous solutions.

 

Formation of IPA

• Formation of IPA reached 50% of maximum or higher within 4, 4 and 1 minutes at pH 4, 7 and 10 at 0°C.

• Formation of IPA reached 50% of maximum or higher within 15 seconds at pH 7 and 25°C.

 

Mass Balance of ICL, Half-Acid, and IPA

• The determination of ICL, Half-acid, and IPA resulted in a mass (material) balance of greater than 95%.

 

Experimental conditions – pH and temperature

• Capacity of the buffers was checked by measuring the pH of the buffers after the acid chloride was added. All buffers showed no significant (± 0.1 pH unit) change in pH.

• The temperature of the water bath used to maintain the test solutions at a constant temperature did not fluctuate significantly at 0 and 25°C (± 0.1°C).

 

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The time in which 50% of the test substance will transform in water at environmentally relevant pH ranges and temperatures is less than 6 minutes (t1/2 < 6 minutes). The final product of ICL hydrolysis is IPA.

Executive summary:

Hydrolysis of ICL was initially performed at pH 7 and 15°C. The concentration of ICL after 30 seconds had decreased by approximately 85% (data not shown) at this temperature and pH. This indicated that hydrolysis occurred quickly and that samples would be difficult to collect at temperatures of 15°C and greater to provide a minimum of six spaced data points between 20 and 70% hydrolysis, as required by OECD guidelines.

The hydrolysis reaction was then performed at pH 4, 7 and 9 at 0°C. Under these conditions ICL also was demonstrated to be hydrolytically unstable. The hydrolysis of the test substance under these conditions, however, was sufficiently slow that a half-life (t½) could be determined, which was less than six minutes.

The time 0 results at pH 4, 7 and 9 verify that formation of the adduct is quantitative. The nominal amount of ICL added at time t = 0 was 10 µg/L. Recoveries at pH 4, 7 and 9 and t = 0 averaged 92, 112, and 92%, respectively, which is within the range of generally acceptable recoveries of 70 to 120% of nominal.

This phase of the hydrolysis study, however, was not designed to determine the products of ICL hydrolysis. Therefore, additional testing was performed at pH 4, 7 and 10 and 0°C to determine the products of ICL hydrolysis. There were changes in conditions for this phase of the study from those of the previous one. The pH buffer compositions were slightly different and the study was performed pH 10 versus 9. Also, a HPLC method was developed to measure Half-acid and IPA that formed from the hydrolysis of ICL. These changes, however, do not materially affect the results of the study.

Finally, experiments were conducted at pH 7 and 25°C. Although hydrolysis at this temperature was too rapid for accurate half-life determinations, these experiments confirmed the increasingly rapid conversion of ICL to its terminal hydrolysis product IPA at an environmentally relevant pH and temperatures greater than 0°C.

Two products of ICL hydrolysis were determined in these additional studies. One is a short-lived intermediate in which one of the two carboxylic acid chloride functionalities of ICL reacts with water to form the carboxylic acid (designated as the Half-Acid). The Half-acid was measured in samples collected at or before one minute of the hydrolysis study at all three pH values and two temperatures. The concentration of the Half-acid attained a maximum concentration and began to decline in samples collected within the first three minutes of the studies conducted at 0°C and within the first 30 seconds at pH 7 and 25°C.

The other product of ICL hydrolysis is IPA. The Half-acid undergoes additional hydrolysis in which the remaining chloride functionality transforms to carboxylic acid to form IPA. The two chloride functionalities in ICL also may undergo simultaneous transformation to IPA. The concentration of IPA attained greater than 50% molar concentration of the ICL initially added within 4 minutes of the start of the studies at all three pH levels and greater than 90% of the ICL initially added within 30 minutes.

 

• Time in which 50% of the test substance will transform in water at environmentally relevant pH ranges and temperatures is less than six minutes (t½ < 6 minutes).

• Half-acid is a short-lived, unstable intermediate product of ICL hydrolysis.

• Final product of ICL hydrolysis is IPA.

• Time in which 50% of the maximum calculated IPA will form in water at environmentally relevant pH ranges and temperatures was less than four minutes.

• Mass (material) balance of the studies was greater than 95% on a molar basis.