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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 23 March 2000 and 11 April 2000.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
EC Number:
938-649-5
Cas Number:
1469982-92-0
Molecular formula:
Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
IUPAC Name:
Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
Details on test material:
Sponsor's identification: PR 4659 SALT
Date received: 3 March 2000
Description: extremely viscous amber liquid
Storage conditions: room temperature in the dark.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Male and female Sprague-Dawley CD (Crl : CD (SD) IGS BR) strain rats supplied by Charles River (UK) ltd, Margate, Kent, UK were used.
- Age at study initiation: Eight to twelve weeks old.
- Weight at study initiation: Males weighed 205 to 215 g and females 210 to 235 g.
- 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 three by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Free access to food.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 19 to 25°C.
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%.
- Air changes (per hr): Approximately fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): Dose volume was 10 ml/kg


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): The test material was freshly prepared, as required, as a solution at the appropriate concentration in distilled water.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The information available suggested a starting dose of 2000 mg/kg.
Doses:
Dose level: 2000 mg/kg
No. of animals per sex per dose:
3 males and 3 females at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 mins, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- Necropsy of survivors performed: yes;
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals, including the female that died, were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

- Other examinations performed: The number of animals dying during the study, or killed for humane reasons, was determined. The nature, severity, time of onset and duration of toxic effects were also determined. Effects on bodyweights and abnormalities noted at necropsy were identified.






Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
Individual mortality data are given in Table 1 (see attached background material).

One female was found dead two days after dosing.
Clinical signs:
Individual clinical observations are given in Tables 2 and 3 (see attached background material).

Clinical signs of toxicity commonly noted were diarrhoea, hunched posture, lethargy, pilo-erection and ptosis with additional incidents of ataxia, decreased respiratory rate, laboured respiration and staining around eyes, mouth and snout.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Tables 4 and 5 (see attached background material).

The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Individual necropsy findings are given in Tables 6 and 7 (see attached background material).

Abnormalities noted at necropsy of the female that died during the study were haemorrhagic lungs, dark liver, dark kidneys and sloughing of the gastric mucosa and non-glandular epithelium of the stomach. White foci in one area of the non-glandular epithelium of the stomach were noted in one male that was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

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 Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

Mortalities were noted at 2000 mg/kg bodyweight.
Executive summary:

Introduction:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

Method:

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted males at the same dose level.

The test material was administered orally as a solution in distilled water. The animals

were observed 30 minutes,1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day a (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period the surviving animals were killed by cervical dislocation and all animals were subjected to gross necropsy.

Results:

One female was found dead two days after dosing.

Clinical signs of toxicity commonly noted were diarrhoea, hunched posture, lethargy, pilo-erection and ptosis with additional incidents of ataxia, decreased respiratory rate, laboured respiration and staining around eyes, mouth and snout.

The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of the female that died during the study were haemorrhagic lungs, dark liver, dark kidneys and sloughing of the gastric mucosa and non-glandular epithelium of the stomach. White foci in one area of the non-glandular epithelium of the stomach were noted in one male that was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Conclusion:

The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

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