N-(tert-butyl)benzylamine

Endpoint summary

Description of key information

Distilled NBTB showed toxicity by the oral route, but showed no systemic toxicity by the dermal route.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study under current quality assurance processes.

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Distilled NBTB, N-Benzyl-tert-butylamine; N-(1,1-dimethylethyl) benzene-methanamine. Purity 99.3% (average). Liquid.

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Margate, Kent, England
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 106-149 g
- Fasting period before study: no data
- Housing:metal cages with wire mesh floors
- Diet (e.g. ad libitum): Lab Sure LAD1 diet, ad libitum
- Water (e.g. ad libitum): municipa, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

gavage using syringes with plastic catheter

Doses:

2000 mg/kg, 500 mg/kg, 250 mg/kg, 100 mg/kg

No. of animals per sex per dose:

Five males and five females at the initial dose of 2000 mg/kg of bodyweight.
Five males and five females at 500 mg/kg of bodyweight
Five males and five females at 400 mg/kg of bodyweight
Five males and five females at 320 mg/kg of bodyweight
Five males and five females at 250 mg/kg of bodyweight.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy with appearance of organs

Statistics:

method of Weil, 1952, Biometrics 8: 249.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

397 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

370 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

432 mg/kg bw

Based on:

test mat.

Mortality:

All rats at dose levels at 400 mg/kg and above died within 3 hours of dosing.

Clinical signs:

other: Salivation, piloerection, pallor of the extremeties, hunched posture, decreased respiratory rate, and lethargy. Additionally, ptosis at 400 mg/kg, body tremors at 250 mg/kg, and prostration at 400 and 500 mg/kg were noted.

Gross pathology:

Autopsy revealed no macroscopic abnormalities among the rats that died.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

The LD50 is between 300 mg/kg and 2000 mg/kg.

Conclusions:

The LD50 of distilled NBTB in female rats was 432 mg/kg, and in males, 370 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

370 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

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:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study under the current standards of quality assurance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Margate, Kent, England
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 200-229 g
- Fasting period before study: no data
- Housing:metal cages with wire mesh floors
- Diet (e.g. ad libitum): Lab Sure LAD1 diet, ad libitum
- Water (e.g. ad libitum): municipa, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 64
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electrical clippers equal to 10% of the total body surface.
The test substance was applied by spreading it evenly over the prepared skin.
The treated area was wrapped in gauze with impermeable dressing around the trunk.

Duration of exposure:

24 hours

Doses:

All rats received one single dose of 2.0g/kg of bodyweight

No. of animals per sex per dose:

5 females
5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 0 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology, other:

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1 male rat died within 24 hours of dosing.

Clinical signs:

other: Abnormal gait was observed in all males and two females. Decreased respiratory rate was observed in two males and two females. Other observations: lethargy, pallor of extremities, lacrymation. Recovery by Day 4.

Gross pathology:

Areas of necrosis and slight to well-defined oedema were apparent on Day 2 at all sites of application of the test substance. Scab formation occurred and scabs detached and show apparently normal skin.

Other findings:

Bruising of subcutaneous tissues at site of application.

The acute lethal dose of NBTB was found to be greater than 2000 mg/kg or 2.0 g/kg body weight. Therefore, it is not toxic via the dermal route.

Interpretation of results:

GHS criteria not met

Conclusions:

NBTB was not found to be toxic via the dermal route at doses higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Additional information

The distilled material showed a LD50 in male rats of 370 mg/kg, and of 432 in female rats. The distilled substance was not systemically toxicity when applied for 4 hours by the dermal route.

Justification for classification or non-classification

With an acute oral toxicity of 370 mg/kg bw in male rats, the substance meets the criteria of Acute Oral Toxicity, Category 4, falling within the criteria of LD50 between 300 and 2000 mg/kg, according to Regulation EC No. 1272/2008.