Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
until 08 May 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
No buffer solution has been used and the test was performed without pH control and at room temperature.
GLP compliance:
no
Remarks:
Test was performed scientifically reasonable and was well-documented, and the sponsor is considered most suitable to perform this test due to the extensive knowledge of the substance, although not having GLP-status.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products / Sampling method: 10 mg of the test substance were dissolved in 2 mL THF and filled up to 100 mL with methanol. 10 mL of this stock solution were transferred into a 1 L volumetric flask and filled up to 1 L with water (c = 1 ppm). This test solution was directly subjected to HPLC measurements about every 20 min in order to follow hydrolysis.
Buffers:
none
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 10 mg of the test substance were dissolved in 2 mL THF and filled up to 100 mL with methanol. 10 mL of this stock solution were transferred into a 1 L volumetric flask and filled up to 1 L with water (c = 1 ppm). This test solution was directly subjected to HPLC measurements about every 20 min in order to follow hydrolysis.
Duration of test
Duration:
12.85 h
Temp.:
20 °C
Initial conc. measured:
1 mg/L
Remarks:
Since the instability of the test substance in water is known a preliminary test was omitted. The test was performed at T = 20 ± 2 °C. The pH value of the test solution was not determined.
Number of replicates:
1
Positive controls:
no
Negative controls:
no
Statistical methods:
In order to determine half-life the logarithmic peak areas normalised to the initial peak area were plotted against time. The quantification was done by area normalisation.

Results and discussion

Test performance:
The HPLC chromatograms showed rapid degradation of the substance in water at room temperature. 1,3,4-Dimercaptothiadiazol (DMTD) and benzoic acid were identified as degradation products as expected by hydrolytical cleavage of the thioester group. The identification of the degradation products was done by diode array detector and comparison of the obtained UV spectra with a spectral library.
For testing of pseudo-first order kinetics the logarithm of the normalised peak area was plotted against time. A linear relationship was obtained (Coefficient of correlation R² = 0.9791). The half-life time of the test item was determined according to the model for pseudo-first order reaction. The slope of the linear regression was constructed excluding the last data points at t = 10.33 min and following.
Transformation products:
yes
Identity of transformation productsopen allclose all
No.:
#1
Reference
Reference substance name:
Unnamed
Inventory number:
InventoryMultipleMappingImpl [inventoryEntryValue=EC 214-014-1]
IUPAC name:
1,3,4-thiadiazole-2,5-dithiol
Identity:
.DELTA.2-1,3,4-Thiadiazoline-5-thione, 2-mercapto-
CAS number:
1072-71-5
Molecular formula:
C2H2N2S3
Molecular weight:
150.246
SMILES notation:
Sc1nnc(S)s1
InChl:
InChI=1/C2H2N2S3/c5-1-3-4-2(6)7-1/h(H,3,5)(H,4,6)
No.:
#2
Reference
Reference substance name:
Unnamed
Inventory number:
InventoryMultipleMappingImpl [inventoryEntryValue=EC 200-618-2]
IUPAC name:
benzoic acid
CAS number:
65-85-0
Molecular formula:
C7H6O2
Molecular weight:
122.121
SMILES notation:
OC(=O)c1ccccc1
InChl:
InChI=1/C7H6O2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H,8,9)
Details on hydrolysis and appearance of transformation product(s):
The hydrolytic degradation of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate can be described as a pseudo-first order kinetic and the half-life of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate was determined to be 1.91 h. 1,3,4-Dimercapto-thiadiazol (DMTD, CAS 1072-71-5) and benzoic acid (CAS 65-85-0) were identified as degradation products as expected by hydrolytical cleavage of the thioester group. No further assessment of the hydrolysis of benzoic acid and DMTD has been conducted because these substances are known to be hydrolytically stable.
Dissipation DT50 of parent compound
Key result
Temp.:
20 °C
Hydrolysis rate constant:
0.36 h-1
DT50:
1.91 h
Type:
(pseudo-)first order (= half-life)
Details on results:
The HPLC chromatograms showed rapid degradation of the substance in water at room temperature. 1,3,4-Dimercaptothiadiazol (DMTD) and benzoic acid were identified as degradation products as expected by hydrolytical cleavage of the thioester group. The identification of the degradation products was done by diode array detector and comparison of the obtained UV spectra with a spectral library.
For testing of pseudo-first order kinetics the logarithm of the normalised peak area was plotted against time. A linear relationship was obtained (Coefficient of correlation R² = 0.9791). The half-life time of the test item was determined according to the model for pseudo-first order reaction. The slope of the linear regression was constructed excluding the last data points at t = 10.33 min and following.

Applicant's summary and conclusion

Validity criteria fulfilled:
not specified
Conclusions:
The study was conducted scientifically reasonable according to OECD TG 111 with minor deviations and is sufficiently documented. Hence, it is sufficiently reliable to assess the hydrolysis behaviour of 5-Mercapto-1,3,4-thiadiazole-2-thiol-benzoate in unbuffered water. The hydrolytic degradation of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate can be described as a pseudo-first order kinetic and the half-life of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate was determined to be 1.91 h. 1,3,4-Dimercapto-thiadiazol (DMTD, CAS 1072-71-5) and benzoic acid (CAS 65-85-0) were identified as degradation products as expected by hydrolytical cleavage of the thioester group. No further assessment of the hydrolysis of benzoic acid and DMTD needed to be conducted because these substances are known to be hydrolytically stable.
It can be concluded that the substance hydrolyzes very rapidly in water, i.e. the half life is max. 1/25 of the test duration when put into aqueous test systems, e.g. daphnia or algae acute toxicity tests. Hence, the substance as such does not need to be tested in those systems, it is sufficient for hazard assessment to use data gained with 1,3,4-Dimercapto-thiadiazol (DMTD, CAS 1072-71-5) and benzoic acid (CAS 65-85-0).
Executive summary:

The substance 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate is known to hydrolyse in aqueous solutions. Thus, a hydrolysis test was performed and hydrolysis products were identified. The test design was according to the principles of the guideline OECD 111. No buffer solution has been used and the test was performed without pH control and at room temperature.

The hydrolytic degradation of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate can be described as a pseudo-first order kinetic and the half-life of 5-mercapto-1,3,4-thiadiazole-2-thiol-benzoate was determined to be 1.91 h. 1,3,4-Dimercapto-thiadiazol (DMTD, CAS 1072-71-5) and benzoic acid (CAS 65-85-0) were identified as degradation products as expected by hydrolytical cleavage of the thioester group. No further assessment of the hydrolysis of benzoic acid and DMTD has been conducted because these substances are known to be hydrolytically stable.