Trihexylamine

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Trihexylamine

EC Number:

203-062-9

EC Name:

Trihexylamine

Cas Number:

102-86-3

Molecular formula:

C18H39N

IUPAC Name:

trihexylamine

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 or test system 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 levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 150 mg/kg bw

Based on:

test mat. (total fraction)

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Effect levels 3

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.