1-Propanamine, 3-(C9-11-isoalkyloxy) derivs., C10-rich

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

January 15, 1985 - January 30, 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Limited reporting. - 3 dose levels: 25, 200 and 2000 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

Test material information

Constituent 1

Reference substance name:

C8-10-Etheramine

IUPAC Name:

C8-10-Etheramine

Details on test material:

- Name of test material (as cited in study report): Etheramine 810
- Molecular formula (if other than submission substance): CH3(CH2)n-O-(CH2)3)-NH2 (n = 7 or 9)
n=7: C8-etheramine, mw = 187.324
n=9: C10-etheramine, mw = 215.378
- Molecular weight (if other than submission substance): 201 (means: about 50% C8-etheramine and 50% C10-etheramione)
- Physical state: Yellow liquid
- Analytical purity: no info
- Impurities (identity and concentrations): octanol and decanol
- Composition of test material, percentage of components: 3-(decyloxy)propylamine and 3-(octyloxy)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 or test system 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 136 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: water, 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):
- Justification for choice of vehicle: no justification, but it is in contrast with info about the insolubility of substance in water and solubility in acetone
- Lot/batch no. (if required): no info
- Purity: no info


MAXIMUM DOSE VOLUME APPLIED: 2.4 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

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 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 all animals died (2 males and 2 females).

Clinical signs:

other: - 25, 200 and 2000 mg/kg: pilo-erection, abnormal body carriage (hunched posture) and increased salivation (shortly after dosing) - 200 and 2000 mg/kg: abnormal gait (waddling), lethargy, decreased respiratory rate and pallor of the extremities - 200 mg/k

Gross pathology:

- Animals that died: Autopsy revealed congestion or haemorrhage of the lungs, pallor of the liver and kidneys and haemorrhage of the stomach
blood vessels.
- 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 C8-10 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 C8-10 was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 25, 200 and 2000 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 mg/kg level all four animals died. Clinical signs of toxicity included pilo-erection, hunched posture and increased salivation accompanied by lethargy, abnormal gait, decreased respiratory rate and pallor of the extremities. Gross pathologic examination on the animals that died showed congestion or haemorrhage of the lungs, pallor of the liver and kidneys and haemorrhage of the stomach blood vessels. Gross pathologic examination at termination revealed nothing remarkable.

Conclusion: The acute oral LD50 of Etheramine 810 for rats is between 200 and 2000 mg/kg of body weight. Confidence limits could not be calculated.

The etheramine is (very) corrosive. The test substance was administrated undiluted at 200 and 2000 mg/kg with 0.24 ml/kg resp. 2.4 ml/kg. Autopsy of the animals that died from 2.4 ml/kg, showed haemorrhage of the stomach. At 0.24 ml/kg the undiluted substance was likely to be just as corrosive locally, however, the volume dose was not sufficient to cause the death of the animals, and they fully recovered. It is uncertain what would happen at 300 mg/kg when 0.36 ml/kg would be dosed, but it is expected that most of the animals would survive this.

Consequently, Etheramine C8-10 is classified for GHS as Toxicity Category 4 with LD50 cut-off of 500 mg/kgbw.