Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 October 1987 to 18 December 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non GLP, acceptable method but essential information in succint report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No certificate of analysis provided
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: not specified
- Expiration date of the lot/batch: not provided in the present report, the study mentionned "a detailed product characterization is included in the raw data"
- Purity test date: data not provided

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
No details on the test item was provided in the report, the study mentionned "a detailed product characterization is included in the raw data"

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not specified
- Females (if applicable) nulliparous and non-pregnant:not applicable
- Age at study initiation: not specified
- Weight at study initiation: 171g
- Fasting period before study: the animals were fasted 16 hours before treatment
- Housing: stainless steel wire mesh cages
- Diet (e.g. ad libitum): Kliba-labordiaet 343, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30 - 70 Relative humidy
- Air changes (per hr): Fully air conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours (6:00 to 18:00 light period)

IN-LIFE DATES: not specified, euthanasia date : 11 November 1987

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: test item at 43.00, 20.00 and 9.28 mg/L for, respectively, doses 2150, 100 and 464 mg/kg bw.
- Amount of vehicle (if gavage): 5 ml/kg
- Justification for choice of vehicle: the test item is insoluble in water
- Lot/batch no. (if required): not specifed
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION (if unusual): not specified
Doses:
464, 1000 and 2150 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose were used.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recording of signs and symptoms several times on the day of administration, at least once each workday. Check for moribund and dead animals twice each workday and once on holidays
- Necropsy of survivors performed: yes, withdrawal of food about 16 hours before sacrifice with CO2 : then necropsy with gross-pathological examination was performed. Necropsy all animals that die was assessed as early as possible

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 150 mg/kg bw
Based on:
test mat. (total fraction)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 150 mg/kg bw
Based on:
test mat.
Remarks on result:
other: value from interpolation
Mortality:
Males : 1 animal died 2 days after exposure in high dose group, all animals of the high dose group died at 14 days.
Females : 2 animals died 2 days after exposure,all animals of the high dose group died at 14 days. 3 animals of the 1000 mg/kg group died after 7 days.
Clinical signs:
Animals of all groups showed dysponea, apathy and piloerection at the low dose level. At medium dose, they additionnaly showed staggering and exsiccosis for male and females. At the high dose, they showed abnormal, atonia, paresis and spastic gait (this symptoms were present in the medium dose group for female animals)
Body weight:
no effect

Any other information on results incl. tables

Table 1 :Results for male rats

Doses (mg/kg)

Number of animals

Dead animals

Mortality(%)

464

5

0

0

1000

5

0

0

2150

5

5

100

 

Table2 :Results for female rats

Doses (mg/kg)

Number of animals

Dead animals

Mortality(%)

464

5

0

0

1000

5

3

60

2150

5

5

100

 

Table 3 : Results for male and females animals (pooled data)

Doses (mg/kg)

Number of animals

Dead animals

Mortality(%)

464

10

0

0

1000

10

3

30

2150

10

10

100

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results, the LD50 of the test item tri-N-hexylamine was defined at 1150 mg/kg for rats by oral gavage. Hence, according to CLP criteria, the tri-n-hexylamine was classified Category 4 for acute oral hazard.
Executive summary:

This non-GLP compliant study was assessed to evaluate the acute oral toxicity of the tri-N-hexylamine when administered in rats by gavage. The method was similar to OECD Guideline 401.

Female and male Wistar rats were used for this study. They were orally treated with 464, 1000 and 2150 mg/kg in single administration. 5 animals were used per condition and per sex. Clinical signs, symptoms and mortality were observed for 14 days.

Clinical signs were observed after treatment. Animals of all groups showed dyspnea, apathy and piloerection at the low dose level. At medium dose, they additionnaly showed staggering and exsiccosis for male and females. At the high dose, they showed abnormal, atonia, paresis and spastic gait (this symptoms were present in the medium dose group for female animals).

For males : 1 animal died 2 days after exposure in high dose group, all animals of the high dose group died at 14 days.

For females : 2 animals died 2 days after exposure,all animals of the high dose group died at 14 days. 3 animals of the 1000 mg/kg group died after 7 days

Based on the results, the LD50  of the test item tri-N-hexylamine was defined at 1150 mg/kg for rats by oral gavage. Hence, according to CLP criteria, the tri-n-hexylamine was classified Category 4 for acute oral hazard.