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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
January 15, 1985 - January 30, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not fully compatible with Guideline 423: 2 male and 2 female animals at each dose level, dose levels 25, 200, 2000 mg/kg, rather then 50, 300, 2000 mg/kg.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Limited reporting. - 4 dose levels, highest is exceptionally: 25, 200, 2000 and 5000 mg/kg - 4 animals: 2 M + 2 F at each dose level - animals aging 4 to 6 weeks
GLP compliance:
yes
Remarks:
audited inhouse
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Etheramine 1215
- Molecular formula (if other than submission substance): CH3(CH2)n-O-(CH2)3)-NH2 (n = 11 - 14)
- Molecular weight (if other than submission substance): no info
- Physical state: Cloudy yellow liquid
- Analytical purity: no info
- Impurities (identity and concentrations): Dobanol 25
- Composition of test material, percentage of components: 3-alkyloxy propylamine
- Purity test date: no info
- Lot/batch No.: no info
- Stability under test conditions: not determined
- Storage condition of test material: stored at ambient temperature
- Other: strongly alkaline

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley obtained from Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks of age
- Weight at study initiation: 100 to 133 g
- Fasting period before study: overnight and approximately 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet (Scientific Feeds LAD 1 obtained from Special Diet Services Ltd., Witham, Essex, England),
ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period:minimum period of 5 days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): min 21 + max 23
- Humidity (%): average 42%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period


IN-LIFE DATES: From: 15 January 1985 To: 30 January 1985

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil, and the other one is unknown (supplied by Sponsor)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 concentrations tested: one as supplied bij Sponsor (unknown vehicle) and one as 25% w/v solution in distilled water
- Amount of vehicle (if gavage): no info
- Justification for choice of vehicle: no justification, but the substance is insoluble in water and soluble in acetone
- Lot/batch no. (if required): no info
- Purity: no info


MAXIMUM DOSE VOLUME APPLIED: 5.75 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no info, just started with lowest dose level
Doses:
Dose levels:
- 25 mg/kg
- 200 mg/kg
- 2000 mg/kg
- 5000 mg/kg
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations after dosing, frequently on Day 1 and on subsequent days at least twice per day. Weighing
on Days 1 (dosing), 4, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (macroscopic post mortem examination)
Statistics:
No statistics.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Remarks on result:
other: No confidence limits
Mortality:
At 2000 mg/kg and 5000 mg/kg all animals died (4 males and 4 females).
Clinical signs:
- 25, 200, 2000 and 5000 mg/kg: pilo-erection, abnormal body carriage (hunched posture) and increased salivation (shortly after dosing)
- 200, 2000 and 5000 mg/kg: abnormal gait (waddling), lethargy and pallor of the extremities
- 2000 and 5000 mg/kg: decreased respiratory rate
- 5000 mg/kg: ptosis
- Recovery as judged by external appearance and behaviour: complete by Day 3 (25 mg/kg) and Day 9 (200 mg/kg).
Body weight:
- Body weight losses were recorded for all rats that died.
- Bodyweight loss for 1 male (dosed 200 mg/kg) on Day 4. Normal bodyweight gain on Days 8 and 15.
- Normal bodyweight gains for the remaining animals on Days 4, 8 and 15.
Gross pathology:
- Animals that died: autopsy revealed haemorrhage and congestion of the lungs and pallor of the spleen, liver and kidneys
- Terminal autopsy findings were normal.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute lethal oral dose to rats of Etheramine C12-15 was found to be: between 200 and 2000 mg/kg bodyweight, with a LD50 cut-off of 500 mg/kgbw.
Executive summary:

The study was performed with similarities to OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method) and according to GLP standards (audited in-house).

The test material, Etheramine C12-15 was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 25, 200, 2000 and 5000 mg/kg to two males and two females. Dosing started with the lowest dose. As no deaths occurred at this level within 24 hours, the next dose was given to another group, and so on. At the 2000 and 5000 mg/kg levels all animals died. Clinical signs of toxicity included pilo-erection, abnormal body carriage and increased salivation accompanied by lethargy, abnormal gait, decreased respiratory rate, pallor of the extremities and ptosis. Gross pathologic examination on the animals that died showed haemorrhage and congestion of the lungs and pallor of the spleen, liver and kidneys. Gross pathologic examination at termination revealed nothing remarkable.

The dose of at 5000 mg/kg did not seem to results to higher toxicity compared to 2000 mg/kg, as time to death was not shorter (actually longer on average.)

The etheramine is (very) corrosive. The test substance was administrated undiluted at 200, 2000 and 5000 mg/kg with 0.23, 2.3 and 5.75 ml/kg respectively. It is uncertain what would happen at 300 mg/kg when 0.35 ml/kg would be dosed, but it is expected that most of the animals would survive this.

Consequently, Etheramine C12-15 is classified for GHS as Toxicity Category 4 with LD50 cut-off of 500 mg/kgbw.