2,4,6-trimethylbenzene-1,3-diamine

Endpoint summary

Description of key information

In this experiment the test item was examined for acute toxicity after oral administration to rats. Dose levels of 300 or 2000 mg/kg b.w. were employed. The LD₅₀value was ranked between 300 and 2000 mg/kg b.w., by oral administration (LPT, 2016).

 

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:

2016-03-17 to 2016-05-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: CD / Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of administration: Approx. 8 weeks
- Weight at start of administration: 178 - 185 g
- Fasting period before study: approx. 16 hours
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated
textured wood was used as bedding material for the cages.
- Diet:Commercial diet, ssniff® R/M-H V1534 (Certificates of analysis provided) ; discontinued approx. 16 hours before administration
- Water: tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 12 to 18-fold air change per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light (about 150 lux at approx. 1.50 m room height)

Route of administration:

oral: gavage

Vehicle:

other: 0.8% aqueous hydroxypropylmethylcellulose

Details on oral exposure:

Vehicle: 0.8% aqueous hydroxypropylmethylcellulose
Route of administration Oral, by gavage
Selection of route of administration According to the OECD/EC guidelines
Vehicle 0.8% aqueous hydroxypropylmethylcellulose
Administration volume 10 mL/kg b.w.
Dose levels 300 and 2000 mg/kg b.w.


CLASS METHOD (if applicable)
Principle of the ATC-test method
This procedure permits the identification of the 'acute-toxic-class' (ATC), a measure-ment of the acute toxicity by the oral route.

The test item is administered orally by gavage at a single dose level to a group of experimental animals. The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.
The test item is tested using a stepwise procedure, each step uses three female animals. The results of each step determine if:
o no further testing is needed,
o the next step will be performed with the same dose,
o the next step will be performed at the next higher or next lower dose level.

Starting at 2000 mg/kg b.w.
If, in this second step, two to three animals die, testing at 300 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.
Testing at 300 mg/kg b.w.:
Three female animals are treated at 300 mg/kg b.w. (first step).
If fewer than two animals die, the test item should be retested (second step) with 300 mg/kg b.w., using three animals of the same sex.

Doses:

300 and 2000 mg/kg b.w.

No. of animals per sex per dose:

3 female animals 2000 mg/kg b.w.
6 female animals 300 mg/kg b.w.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours
after administration. All surviving animals were observed for a period of 14 days. Individual body weights were recorded before administration
of the testsubstance and thereafter in weekly intervals up to the end of the study.

- Necropsy of survivors performed: At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross
pathological changes were recorded.

- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory,autonomic and central
nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter
each working day. Any tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma were also noted.

Statistics:

No statistical analysis was performed as the method used is not intended to allow a calculation of a precise LD50 value.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

Under the present test conditions, oral administration of 2000 mg test item/kg b.w. revealed lateral position in all 3 of three animals. All 3 animals died within 24 hours after administration

Clinical signs:

other: Oral administration of 300 mg test item/kg b.w. revealed slightly reduced motilitly, slight ataxia, slightly reduced muscle tone, slight dyspnoea in all 6 of 6 animals, closed eyes in 5 of 6 animals and dorsal position in 1 of 6 animals. One animal died w

Gross pathology:

No pathological changes were observed at necropsy.

Other findings:

- Histopathology:
No histopathology was carried out as no macroscopical findings were noted at autopsy.

no further information

Conclusions:

The LD50 value was ranked between 300 and 2000 mg/kg b.w.

Executive summary:

In this experiment the test item was examined for acute toxicity after oral administration to rats. Dose levels of 300 or 2000 mg/kg b.w. were employed.

Under the present test conditions, oral administration of 2000 mg test item/kg b.w. revealed lateral position in all 3 of three animals. All 3 animals died within 24 hours after administration.

Oral administration of 300 mg test item/kg b.w. revealed slightly reduced motilitly, slight ataxia, slightly reduced muscle tone, slight dyspnoea in all 6 of 6 animals, closed eyes in 5 of 6 animals and dorsal position in 1 of 6 animals. One animal died within 7 days after administration.

All surviving animals gained the expected weight at the end of the study period.

No pathological changes were observed at necropsy.

The LD₅₀value was ranked between 300 and 2000 mg/kg b.w., by oral administration.

 

Test item

LD50[mg/kg b.w., oral]

females

300 - 2000

 

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

The study is valid without restriction (Klimisch 1).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of the acute oral study and according to the Globally Harmonized Classification System (GHS) the test item is classified in the hazard category 4, required labelling with 'Warning' and 'Harmful if swallowed'. According to the EC Regulation 1272/2008 and subsequent regulations, the test item required labelling with 'Warning' and 'H302: Harmful if swallowed'.