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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 20 September 2007 and 17 October 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of N,N’-bis-(3-methoxypropyl)-C22(branched)-alkyldiamide and N,N’-bis-(3-methoxypropyl)-C17(branched)-alkyldiamide
EC Number:
940-953-8
Molecular formula:
not applicable UVCB
IUPAC Name:
Reaction mass of N,N’-bis-(3-methoxypropyl)-C22(branched)-alkyldiamide and N,N’-bis-(3-methoxypropyl)-C17(branched)-alkyldiamide
Test material form:
other: off white waxy solid block

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Female Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd.
- Age at study initiation: Eight to twelve weeks of age.
- Weight at study initiation: 202 g to 247 g at Day 0. The bodyweight variation did not exceed ± 20% of the initial mean bodyweight of any previously dosed animal(s).
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Free access to food (Certified Rat and Mouse Diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 to 25°C.
- Humidity (%): Set to achieve limits of 30 to 70%.
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE:
- Concentration in vehicle: 30 mg/ml (for 300 mg/kg dose level) and 200 mg/ml (for 2000 mg/kg dose level).

- Justification for choice of vehicle: Dimethyl sulphoxide was used because the test material did not dissolve/suspend in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION: For the purpose of the study the test material was freshly prepared, as required, as a solution dimethyl sulphoxide.

PROCEDURE:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

A single animals was treated at a dose level of 300 mg/kg.
In the absence of toxicity at a dose level of 300 mg/kg, an additional animal was treated at a dose level of 2000 mg/kg.
In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of 4 animals were treated at a dose level of 2000 mg/kg.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
1 animal at 300 mg/kg and 5 animals at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:
Dose Level of 300 mg/kg with a single animal:
There was no death. No signs of systemic toxicity were noted during the observation period. The animals showed expected gains in bodyweight over the observation period. No abnormalities were noted at necropsy.
Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main test.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose Level: 2000 mg/kg
There were no deaths.
Clinical signs:
Dose Level: 2000 mg/kg
No signs of systemic toxicity were noted during the observation period.
Body weight:
Dose Level: 2000 mg/kg
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
Dose Level: 2000 mg/kg
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" ( 2001)

- Method Bl bis Acute Toxicity ( Oral) of Commission Directive 2004/73/EC

Method.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a solution in dimethyl sulphoxide, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight

development were monitored during the study. All animals were subjected to gross necropsy.

Mortality.

There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity.

Bodyweight.

All animals showed expected gains in bodyweight.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.