reaction mass of 1-[2-(2-aminobutoxy)ethoxy]but-2-ylamine and 1-({[2-(2-aminobutoxy)ethoxy]methyl}propoxy)but-2-ylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2011-12-05 to 2011-12-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

relative humidity 18 to 61%, 1 animal not weighed at time of death

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): XTJ-568
- Substance type: Clear colorless liquid
- Physical state: liquid
- Analytical purity: 97% (primary amine)
- Composition of test material, percentage of components: water (0.03%), acetylatable (9.2 meq/g), total amine (8.7 meq/g)
- Lot/batch No.: 0G704
- Stability under test conditions: no data
- Storage condition of test material: 21 - 26.7°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan
- Age at study initiation: 9 to 10 weeks at start of dosing; records of dates of birth for animals used in this study are retained in the Calvert archives.
- Weight at study initiation: 191 - 202 grams
- Fasting period before study: Animals were fasted overnight prior to dose administration.
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council " Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals were kept was documented in the study records. no other species were kept in the same room.
- Diet (e.g. ad libitum): ad libitum with fasting overnight prior to dose administration
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22°C
- Humidity (%): 18 to 61%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Dose preparation: An initial preparation of the test article in distilled water resulted in an undoseable suspension with a pH of 13. Therefore, the proper amount of the test article was measured according to volume since it was a liquid, and was allocated/dosed neat as received from the Sponsor with a pH of 10. The stock bottle was inverted several times prior to dispensing.

Dose volumes (specific density 1 g/ml): 0.32, 0.55, 1 and 2 ml/kg.

Doses:

320, 550, 1000 or 2000 mg/kg

No. of animals per sex per dose:

A total of six rats received the substance.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality/morbidity: manually recorded once daily
clinical observations: clinical observations were collected manually. On the day of dosing (Day 1) animals were observed prior to dosing and approximately 30 minutes and 4 hours post-dose. Animals were observed once daily thereafter (Days 2-15).
body weight: Animal weights were manually recorded prior to dosing on Day 1, and on Day 8 and 15, or upon death.
- Necropsy of survivors performed: yes. The necropsy included examination of: the external body surface, all orifices, the cranial, thoracic and abdominal cavities and their contents. All surviving animals were euthanized by CO2 asphyxiation.

Statistics:

The LD50 was calculated for the main test using AOT425StatPgm developed by Westat May, 2001.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

95% CL:

>= 275.7 - <= 2 580

Mortality:

Mortality was not observed in any of the animals dosed at 320 or 550 mg/kg of the substance. Two of three animals receiving the test article at 1000 mg/kg were found dead as well as the single animal dosed at 2000 mg/kg.

Clinical signs:

other: Clinical observations observed included piloerection at 30 minutes in the single animal at 320 mg/kg and in the surviving animal at 1000 mg/kg. no clinical signs were observed prior to death in the two other animals at 1000 mg/kg. Piloerection, decreased

Gross pathology:

Terminal necropsy revealed no visible lesions in the animals at 320, 550 or the surviving animal at 1000 mg/kg. Necropsy of two animals found dead at 1000 and 2000 mg/kg revealed dark red fluid-filled intestines. The third animal found dead had no visible lesions.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of this study, the oral LD50 for the substance in rats was estimated to be 1000 mg/kg (95% PL Confidence interval of 275.7 to 2580 mg/kg). The substance is considered classified as acute oral toxicant category 4 according to the criteria laid down in the CLP Regulation (EC) 1272/2008.