2,4,6-trinitrobenzene-1,3,5-triamine

Endpoint summary

Description of key information

Oral LD50(rats) > 5000 mg/kg bw (OECD 401, WoE, Rel.2)

Oral LD50(mice) > 5000 mg/kg bw (OECD 401, WoE, Rel.2)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Test substance was administered to fasted rats as a suspension in corn oil.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 2 weeks
- Frequency of observations and weighing: After treatment, all animals were observed daily for physiological and behavioural responses. Body weights were recorded initially and weekly thereafter.
- Necropsy of survivors performed: Yes; at the end of the 2-week observation period, all surviving animals were sacrificed and examined for evidence of gross pathological changes.

Statistics:

None

Preliminary study:

Range-finding study results not reported.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: All animals appeared to be normal throughout dosing and during the post-treatment observation period.

Gross pathology:

No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test substance is higher than 5000 mg/kg bw therefore it is not classified for acute oral toxicity according to the CLP Regulation EC No. (1272/2008) and to the GHS.

Executive summary:

In an acute oral toxicity study, Sprague-Dawley rats (10 animals/sex/dose) were given a single oral (gavage) dose of test substance at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 2 -weeks and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortalities occurred and no signs of systemic toxicity were observed during the 14-day observation period. All animals showed body weight gain during the study period. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Under the test conditions, the oral LD50 of the test substance is higher than 5000 mg/kg bw therefore it is not classified for acute oral toxicity according to the CLP Regulation EC No. (1272/2008) and to the GHS.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: ICR/SIM

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 2 weeks
- Frequency of observations and weighing: After treatment, all animals were observed daily for physiological and behavioural responses. Body weights were recorded initially and weekly thereafter.
- Necropsy of survivors performed: Yes; at the end of the 2-week observation period, all surviving animals were sacrificed and examined for evidence of gross pathological changes.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: All male mice had a rough hair coat during the first 4 days post-treatment, but the coat returned to normal thereafter. The females showed no adverse effects throughout the study.

Gross pathology:

No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test substance is higher than 5000 mg/kg bw therefore it is not classified for acute oral toxicity according to the CLP Regulation EC No. (1272/2008) and to the GHS.

Executive summary:

In an acute oral toxicity study, ICR/SIM mice (10 animals/sex/dose) were given a single oral (gavage) dose of test substance at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 2 -weeks and at the end of the study the surviving animals were sacrificed for macroscopic examination.

 

No mortality was observed. All male mice had a rough hair coat during the first 4 days post-treatment, but the coat returned to normal thereafter. The females showed no adverse effects throughout the study. All animals showed body weight gain during the study period. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

 

Under the test conditions, the oral LD50 of the test substance is higher than 5000 mg/kg bw therefore it is not classified for acute oral toxicity according to the CLP Regulation EC No. (1272/2008) and to the GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The two weight of evidence studies are of good quality (Klimisch score = 2)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two studies were identified and used in a weight of evidence approach (Newell, 1976a ; Newell, 1976b).

In the first acute oral toxicity study performed similarly to the OECD guideline No. 401, Sprague-Dawley rats (10 animals/sex/dose) were given a single oral (gavage) dose of test substance at 5000 mg/kg bw.

In the second study, ICR/SIM mice (10 animals/sex/dose) were exposed in the same manner.

There were no deaths during both studies.

All male mice had a rough hair coat during the first 4 days post-treatment, but the coat returned to normal thereafter.

All rats and female mice showed no clinical signs.

All animals showed expected gains in bodyweight over the study period.

No gross abnormalities were noted for the animals necropsied at the conclusion of the study.

Oral LD50 > 5000 mg/kg bw

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 and to the GHS as the LD50 is greater than 5000 mg/kg bw (GHS criteria not met).

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw ≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.