Registration Dossier

Administrative data

Description of key information

Acute Toxicity:

Acute Toxicity: oral (gavage), male Sherman-Wistar albino rats, 5/group: LD50 = 930 mg/kg (660-1310 95%CL) (DMTD, similar to OECD 401)

Acute Toxicity: oral (gavage), male Sherman-Wistar albino rats, 5/group: LD50 = 2955 mg/kg (NATD, 16 CFR Sec. 1500.3)

Acute Toxicity: dermal, semi‑occluded, 24h exposure, 2000 mg/kg undiluted, female Wistar rats: LD50 >2000 mg/kg (0/3 deaths at 2000mg/kg); very slight to well defined erythema and very slight edema. Crust formation, small superficial scattered scabs, scab lifting to reveal glossy skin, yellow staining of the treatment sites(DMTD, OECD 402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980-09-24 - 1980-10-15 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No guideline stated, given information allows the conclusion the study was well performed similar to adopted guidelines.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Sherman-Wistar albino rats
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-300g
- Fasting period before study: The rats were deprived of food but not water overnight prior to dosing.
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CPR Part 3.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% w/v suspension in corn oil
Doses:
0.25, 0.50, 1.0, 2.0, 4.0 g/kg
No. of animals per sex per dose:
5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality daily, weight at the beginning and after 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight
Statistics:
The LD50 was calculated employing the Thompson Moving Average Method as modified by Weil, (Biometrics, September, 1952, Vol. 8, No. 3, page 249-263).
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
930 mg/kg bw
Based on:
test mat.
95% CL:
>= 660 - <= 1 310
Mortality:
Observed, 3/5 rats at 2 g/kg, 5/5 at 4 g/kg
Clinical signs:
0.25 gm/kg: No untoward symptoms were observed.
0.50 gm/kg: No untoward symptoms were observed during the first 4-6 hours. After 24 hours the animals were slightly ruffled and dirty . They appeared normal within 48 hours.
1.0 gm/kg: After 4-6 hours the animals appeared slightly ruffled. They were lethargic and dirty after 24 hours. Within 48 hours they appeared essentially normal.
2.0 gm/kg: After 2-4 hours the animals were slightly depressed and ruffled. Their general condition had worsened after 24 hours with greater depression and ataxia being evident. Within 48 hours some of the animals appeared moribund. Deaths occurred as noted on the third day and the remaining animals were in poor health. An additional death occurred on the fifth day. The two surviving animals appeared essentially recovered after 7-8 days.
4.0 gm/kg: After 2 hours the animals were severely depressed. Several animals became semi-comatose after 6 hours. Deaths occurred over several days as noted.
Body weight:
no effects stated
Gross pathology:
Gross pathologic examination of the 4 g/kg group revealed nothing remarkable.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Study was performed scientifically reasonable similar to OECD TG 401 on 1,3,4-Thiadiazole-2,5-dithiole, and is sufficiently documented. Hence, the results can be considered as reliable to assess the acute oral toxicity of 1,3,4-Thiadiazole-2,5-dithiole towards rats. The LD50 was determined as 0.93 (0.66 - 1.31) g/kg, which is within the boundary values of 300 and 2000 mg/kg, which triggers according to Regulation 1272/2008 the classification as acute toxic Cat. 4.
Executive summary:

In an acute oral toxicity study similar to OECD 401, groups of fasted, male Sherman-Wistar rats (5/group) were given a single oral dose of 1,3,4-Thiadiazole-2,5-dithiole, 50% in corn oil at doses of 250, 500, 1000, 2000, 4000 mg/kg bw and observed for 14 days.

The LD50 was determined as 0.93 (0.66 - 1.31) g/kg in males .

1,3,4-Thiadiazole-2,5-dithiole is of slight Toxicity based on the LD50 in males and needs to be classified as acute toxic oral Cat. 4.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1980-09-19 - 1980-09-24 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Documentation poorer compared to recent standards, but given information allows the conclusion the study was well performed, read-across
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The rational for the analogue approach is the high structural similarity between the source and the target substance. The source chemical is the disodium salt of the registered substance. The organic structure hence is identical, the only difference is the ionisation of the nitrogen with sodium as counterions compared to the hydrogen bound to the nitrogen of the target (registered) substance. Further, when brought into acidic environment, a at least partial ionisation can be expected. Hence, data on disodium 1,3,4-thiadiazole-2,5-dithiolate can be used to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself serve as a worst case for hazard assessment. Due to the similarities in structure, similar physico-chemical properties of the substances are to be expected, which would result in a similar toxicokinetic behaviour and most likely also in very similar toxicodynamic and toxicological behaviour.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: disodium 1,3,4-thiadiazole-2,5-dithiolate, CAS 55906-42-8, SMILES Code [Na+].[Na+].S=C1[N-][N-]C(=S)S1, MW = 194.2 g/mol
Target chemical: 1,3,4-thiadiazole-2,5-dithiol, CAS 1072-71-5, SMILES Code S=C1N=NC(=S)S1, MW = 150.2 g/mol

3. ANALOGUE APPROACH JUSTIFICATION
It is aimed to use data on disodium 1,3,4-thiadiazole-2,5-dithiolate to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself are reliable, serve as a worst case for hazard assessment, no hence not underestimate a potential hazard and no further testing is required. As indicated under point 4 Data Matrix, both substances are small molecules with a negative estimated logPow and a high water solubility, indicating a similar absorption and distribution pattern in the body. Both substances are not irritating to the skin, which was not only shown in a dermal irritation study but further also for CAS 1072-71-5 in a skin sensitization study, which was also negative. Due to the similar behaviour on the skin, it can be concluded that CAS 55906-42-8 would also have been tested negative as a skin sensitizer, and the present study on the target substance CAS 1072-71-5 suffices for hazard assessment. CAS 1072-71-5 should be classified as acute tox. oral Cat. 4, whereas the RA substance CAS 55906-42-8 does not need to be classified, clearly showing that the available study on the registered substance itself does not underestimate a possible hazard. Similar applies to eye irritation, CAS 1072-71-5 must be classified as eye dam. Cat. 1, CAS 55906-42-8 does not.

4. DATA MATRIX
The following table shows the available data relevant to justify the read-across from the source to the target chemical to demonstrate that the available studies on the registered substance itself do not underestimate a possible hazard for the endpoints acute toxicity oral, skin and eye irritation, and skin sensitization:

Endpoint Source: CAS 55906-42-8 Target: CAS 1072-71-5
Molecular weight 194.2 g/mol 150.2 g/mol
Physical state solid solid
Partition coefficient logPow = -2.3734 (EpiSuite estimation) logPow = -0.6349 (EpiSuite estimation)
Water solubility 1e+006 mg/L 2.638e+005 mg/L
Acute toxicity oral LD50 = 2955 mg/kg (rat) LD50 = 930 mg/kg (rat)
Skin irritation Not irritating (in vivo, rabbit) Not irritating (in vivo, rabbit)
Eye irritation Not irritating (in vivo, rabbit) Eye Dam. Cat. 1 (in vivo, rabbit)
Skin sensitization n/a Not sensitizing, not a skin irritant
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other:
Version / remarks:
The method employed in the testing, evaluation and the scoring of the results was similar to that described in Section 1500.3 Federal Hazardous Substances Act Regulations ― 16 CFR - P.114
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: albino rats of the Sherman-Wistar Strain
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: The rats were deprived of food but not water overnight prior to dosing.
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94̶-279) 9 CFR Part 3.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1, 2, 4, 8, 16 g/kg
No. of animals per sex per dose:
5 males per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily (mortality), 1st & last day (body weight)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 was calculated employing the Thompson Moving Average Method as modified by Weil, (Biometrics, September, 1952, Vol. 8, No. 3, page 249-263).
Key result
Sex:
male
Dose descriptor:
LD50
Remarks:
test material
Effect level:
9 850 mg/kg bw
Based on:
test mat.
95% CL:
>= 7 460 - <= 12 990
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 955 mg/kg bw
Based on:
act. ingr.
Remarks:
solid disodium 1,3,4-thiadiazole-2,5-dithiolate
Mortality:
One death occurred after 6 hours in the 8 g/kg group, all animal in the 16 g/kg group died within 6 hours.
Clinical signs:
8.0 gm/kg: After 1-2 hours the animals were depressed, ruffled and ataxic. One death occurred after 6 hours. Within 24 hours the surviving animals appeared essentially normal.
16.0 gm/kg: Within 1 hour the animals were depressed, ruffled and ataxic. Most of the animals were comatose after 3-4 hours and deaths generally occurred in less than 6 hours.
Body weight:
no relevant differences noted
Gross pathology:
Gross pathologic examination revealed nothing remarkable.
Interpretation of results:
GHS criteria not met
Conclusions:
Study was performed scientifically reasonable according to Section 1500.3 Federal Hazardous Substances Act Regulations ― 16 CFR - P.114 on a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate, and is sufficiently documented. Hence, the results can be considered as reliable to assess the acute oral toxicity of disodium 1,3,4-thiadiazole-2,5-dithiolate towards rats. The LD50 was determined as 9850 (7460 - 12990) mg/kg of the 30% aqueous solution, which corresponds to a LD50 = 2955 mg/kg of pure disodium 1,3,4-thiadiazole-2,5-dithiolate. This value is above the limit value of 2000 mg/kg, which triggers according to Regulation 1272/2008 the classification as acute toxic, hence, disodium 1,3,4-thiadiazole-2,5-dithiolate does not need to be classified.
Executive summary:

In an acute oral toxicity study according to Section 1500.3 Federal Hazardous Substances Act Regulations ― 16 CFR - P.114, groups of fasted, male Sherman-Wistar rats (5/group) were given a single oral dose of on a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate at doses of 1000, 2000, 4000, 8000, 16000 mg/kg bw and observed for 14 days.

The LD50 was determined as 9850 (7460 - 12990) mg/kg of the 30% aqueous solution in males, which corresponds to a LD50 = 2955 mg/kg of pure disodium 1,3,4-thiadiazole-2,5-dithiolate.

Disodium 1,3,4-thiadiazole-2,5-dithiolate is of low Toxicity based on the LD50 in males and does not need to be classified as acute toxic oral.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
930 mg/kg bw
Quality of whole database:
There are two sufficiently reliable Klimisch 2 studies (1 on a read-across substance), performed similar to recent guidelines, hence, the database is of high quality.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.
Analysis of the particle size distribution revealed that 5.14% of the particles are 10-100 µm (inhalable fraction), 0.03% 4-10 µm (thoracic), and 0.00% <4 µm (respirable). So the thoracic and respirable fraction does not need to be regarded, and only a very minor portion of the substance is inhalable at all. Inhalation of this minimal fraction is excluded by appropriate organisational measures (see respective section). In addition, with a very low vapour pressure of 1.3 x 10E-04 hPa at 20°C, 2.6 x 10E-04 hPa at 25°C and 5.7 x 10E-03 hPa at 50°C, the substance does not need to be regarded as volatile, and inhalation of vapours can be excluded. Last but not least, the substance is a solid, so no aerosols or droplets need to be considered.
In summary, exposure of humans via inhalation is unlikely, so acute inhalation testing can be omitted.

The registrant concludes further that testing is scientifically not necessary and would not reveal any additional information which cannot be derived from other available acute toxicity data, so that testing can be omitted due to animal welfare:
The design of an OECD 403 study (5 mg/l actual concentration of respirable substances) may overestimate the actual exposure, if it would be possible anyway to convert the substance into an inhalable form.
Further, there are no signs of toxicity obvious via the dermal route, and the oral LD50 is 930 mg/kg. There is no study available fulfilling the criteria of an OECD 403 study (and required) for the acute inhalation toxicity of the test item; however, there is other information on acute toxicity in rats available:

Acute toxicity study similar to OECD 401: LD50 =930 mg/kg
Acute toxicity study dermal, acc. OECD 402: LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg, no deaths occurred, no signs of systemic toxicity were noted during the observation period.

As outlined in detail in the subchapter “Toxicokinetics”, the absorption rates may be estimated to:
Absorption via oral route: 100%
Absorption via inhalative route: 10%
Absorption via dermal route: 50%

According to OECD guideline 403 (Acute inhalation toxicity), the concentration of respirable particles for limit testing is 5 mg/L over 4 h. Taking into account for rats a standard respiratory volume of 0.2 l/min and average body weight of 250 g (Guidance on information and requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, ECHA, http://echa.europa.eu/web/guest/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment), a total respiratory volume of 48 litre over 4 h can be assumed. This would result in a total dose of 240 mg per rat, which is equivalent to 960 mg/kg bw.

Taking into account the estimated absorption rates, it can be clearly concluded that any toxicologically relevant amounts can be absorbed. Assuming in a worst-case scenario, although not relevant based on the phys.-chem. properties of the substance, that this total dose will be absorbed to 100%, this dose would correspond to the actually determined oral LD50, and as 960 mg/kg bw corresponds to the limit dose of 5 mg/L over 4 h in an inhalation study, an LC50 equal to the limit dose could be assumed. So even in a worst-case approach, no classification would be triggered. It can be reasonably assumed that an additional acute toxicity test via the inhalation route would reveal an LC50inhalation ≥ 5 mg/l.

So, in summary, it can be reasonably assumed that an additional testing for acute inhalation toxicity would not reveal any further relevant information or trigger classification as acutely toxic via the inhalation route, and consequently, testing can be omitted due to animal welfare.
Reason / purpose:
data waiving: supporting information
Remarks:
Particle size distribution
Reason / purpose:
data waiving: supporting information
Remarks:
vapour pressure
Reason / purpose:
data waiving: supporting information
Remarks:
appearance
Reason / purpose:
data waiving: supporting information
Remarks:
absorption rates
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-01-24 - 2018-02-14 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guideline for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (2017)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: approximately 4 °C in the dark
Species:
rat
Strain:
Wistar
Remarks:
Wistar (RccHan(TM):WIST)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: At the start of the study the animals were 8 to 12 weeks of age.
- Weight at study initiation: At the start of the study the animals weighed at least 200 g. The weight variation did not exceed ±20% of any previously treated animal.
- Fasting period before study: no
- Housing: The animals were individually housed throughout the study in suspended solid floor polypropylene cages furnished with woodflakes. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 19 to 25 °C.
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
skin was moistened ahead with arachis oil BP
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24 Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: no
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 in total
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2, 4 and 6 hours after dosing and subsequently once daily for 14 days.
After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation
Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: clinical signs, body weight, skin reactions
Preliminary study:
no mortalities noted in the first female
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: none of the three animals died
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
One animal showed body weight loss during the first week with expected gain in body weight during the second week. The remaining animals showed expected gains in body weight.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions:
Signs of dermal irritation noted included very slight to well defined erythema and very slight edema. Crust formation, small superficial scattered scabs and scab lifting to reveal glossy skin were also noted. Yellow staining of the treatment sites was also noted.
Interpretation of results:
GHS criteria not met
Remarks:
EU implementation
Conclusions:
The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats. The acute dermal median lethal dose (LD50) of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.
Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat according to OECD TG 402 under GLP.

Methods: Initially, one female animal was given a single, 24 hour, semi‑occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Based on the results of the initial test, a further two female animals were similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results:

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Signs of dermal irritation noted included very slight to well defined erythema and very slight edema. Crust formation, small superficial scattered scabs and scab lifting to reveal glossy skin were also noted. Yellow staining of the treatment sites was also noted. 

Body Weight. One animal showed body weight loss during the first week with expected gain in body weight during the second week. The remaining animals showed expected gains in body weight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion: The acute dermal median lethal dose (LD50) of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
There is a OECD 402 study under GLP available, assessed with Klimisch 1, hence, the database is of high quality.

Additional information

Justification for classification or non-classification

The LD50 was determined as 0.93 (0.66 - 1.31) g/kg in the acute oral toxicity study on DMTD, which is within the boundary values of 300 and 2000 mg/kg, which triggers according to Regulation 1272/2008 the classification as acute toxic Cat. 4. In the OECD 402 study on DMTD, the LD50 was determined to be > 2000 mg/kg, which is above the limit value for classification.