A mixture of: 3,5-dimethylthio-2,4-toluenediamine; 3,5-dimethylthio-2,6-toluenediamine

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

EEC B.1, EPA 560/6-83-001

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

- Range-finding test: 500, 3200 and 5000 mg/kg
- Main study: 1000, 1250, 1600 and 2500 mg/kg

No. of animals per sex per dose:

- Range finding test: 3 groups of 2 animals (1 M, 1 F)
- Main study: 4 groups of 10 fasted rats (5M, 5F)

Control animals:

no

Preliminary study:

A dose range finding study was performed using 3 groups of 2 animals (1 M, 1 F). Animals were administered test compound at 500, 3200 and 5000 mg/kg by oral gavage. None of the rats died at 500 mg/kg. All of the rats died at the other two dose groups. In the definitive study, 4 groups of 10 fasted rats (5M, 5F) were orally administered the test article at 1000, 1250, 1600 and 2500 mg/kg.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 515 mg/kg bw

95% CL:

>= 960 - <= 2 048

Mortality:

Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1250 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1600 mg/kg bw; Number of animals: 5; Number of deaths: 4
Male: 2500 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 1250 mg/kg bw; Number of animals: 5; Number of deaths: 2
Female: 1600 mg/kg bw; Number of animals: 5; Number of deaths: 3
Female: 2500 mg/kg bw; Number of animals: 5; Number of deaths: 5

Clinical signs:

other: Signs of toxicity related to dose levels: A dose range finding study was performed using 3 groups of 2 animals (1M, 1F). Animals were administered test compound at 500, 3200 and 5000 mg/kg by oral gavage. None of the rats died at 500 mg/kg. All of the ra

Gross pathology:

Effects on organs:
a) 1000, 1250 and 1600 dose levels

Necropsy of animals dying in study revealed hemorrhagic stomach lesions, discolored lungs, hydrothorax, discolored fluid-filled bladders

b) 2500 mg/kg dose level

No visible lesions observed in any animal at terminal necropsy

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity LD50 was found to be 1515 mg/kg bw for males/females. In conclusion, the test substance has to be classified Toxicity Category IV based on the results of this test.

Executive summary:

The acute oral toxicity on rats was determined in a GLP study according to OECD guideline 401 and EU test method B.1. Vehicle was corn oil. A dose range finding study was performed using 3 groups of 2 animals (1 M, 1 F). Animals were administered test compound at 500, 3200 and 5000 mg/kg by oral gavage. None of the rats died at 500 mg/kg. All of the rats died at the other two dose groups. In the definitive study, 4 groups of 10 fasted rats (5M, 5F) were orally administered the test article at 1000, 1250, 1600 and 2500 mg/kg.

Signs observed were decreased activity, ptosis, piloerection, decreased muscle tone, abnormal gait, abnormal stance, poor grooming, diarrhea, chromodacryorrhea and prostration. One of 10 died at 1000 mg/kg, 2110 at 1250 mg/kg, 7110 at 1600 mg/kg and 9/10 at 2500 mg/kg. Necropsy of dead animals revealed hemorrhagic lesions in the stomach, discolored intestines, discolored lungs, hydrothorax and discolored fluid filled bladders.

The acute oral toxicity LD50 was found to be 1515 mg/kg bw for males/females. In conclusion, the test substance has to be classified Toxicity Category IV based on the results of this test.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 515 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

EEC B.3

GLP compliance:

yes

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No signs. None of the rabbits died throughout the study.

Gross pathology:

Effects on organs:
No test article related lesions observed.

Other findings:

Signs of toxicity (local):
Slight to moderate erythema was observed at 24 hours after initiation of exposure (exposure time was 24 hrs.)

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to OECD guideline 402 the acute dermal LD50 was determined to be > 2000 mg/kg. Thus, the test substance can be considered as not acutely toxic via the dermal route.

Executive summary:

According to OECD Guideline 402 the test material was applied at a dose of 2000 mg/kg to five male and five female rabbits. The substance was left in contact with the skin for 24 hours. None of the rabbits died during the study, slight to moderate erythema was observed in every animal at 24 hours after initiation of exposure. No test article related lesions observed in gross pathology. The acute dermal LD50 was determined to be greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Available study

Justification for selection of acute toxicity – dermal endpoint
Available study

Justification for classification or non-classification

The acute oral toxicity LD50 was found to be 1515 mg/kg bw for male/female rats. In conclusion, the test substance has to be classified Toxicity Category IV based on the results of this test.