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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 3 March 2011 to March 29, 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: EU Method and GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

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:
yes

Test material

Constituent 1
Reference substance name:
Amides, C12-14 (even numbered), N-[3-(dimethylamino) propyl], N'-oxides
IUPAC Name:
Amides, C12-14 (even numbered), N-[3-(dimethylamino) propyl], N'-oxides
Details on test material:
- Name of test material (as cited in study report): Amides, C12-14 (even numbered), N-[3-(dimethylamino) propyl], N'-oxides
- Physical state: clear colourless liquid
- Analytical purity: 33%
- Lot/batch No.: 264176.T0694
- Expiration date of the lot/batch: 3 September 2011
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 180-186 g
- Fasting period before study: overnight fast immediately before dosing.
- Housing: in groups of up to four in suspended solid-flood polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (with the exception of the 3-4 hours fast period after dosing). 2014 Teklad Global Rodent diet.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25ºC
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15 changes / hour
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light (06:00 to 18:00 h).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
6.13 ml/kg (6061 mg/kg bw dose level, equivalent to 2000 mg active ingredient/kg bw)
0.93 ml/kg (910 mg/kg bw dose level, equivalent to 300 mg active ingredient/kg bw)

Doses:
6061 mg/kg of the test item (equivalent to 2000 mg active ingredient/kg bw)
910 mg/kg of the test item (equivalent to 300 mg active ingredient/kg bw)
No. of animals per sex per dose:
Group 1 (2000 mg active ingredient/kg bw): 1
Group 2 (300 mg active ingredient/kg bw): 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were made ½, 1, 2 and 4 hours after dosing and then daily for up to 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 or at death.
- Necropsy of survivors performed: yes, by cervical dislocation. 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

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
910 - 6 061 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Equivalent to 300-2000 mg active ingredient/kg bw
Mortality:
The animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw) was found dead one day after dosing. There were no deaths at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw).
Clinical signs:
Exophthalmos and hunched posture were noted in the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw). Signs of systemic toxicity noted in the initial animal treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw) were hunched posture, noisy respiration and pilo-erection. There were no signs of systemic toxicity noted in the additional four animals treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw).
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw), that died during the study, were dark liver, dark kidneys, gaseous distension and dark brown coloured liquid present in the stomach and haemorrhage of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test item in rats was estimated to be in the range of 910-6061 mg/kg bw (equivalent to 300-2000 mg active ingredient/kg bw).
Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with OECD Guideline 420 “Acute Oral Toxicity - Fixed Dose Method” and EU Method B1 bis Acute Toxicity (Oral).

Following a sighting test at dose levels of 6061 mg/kg and 910 mg/kg (equivalent to 2000 and 300 mg active ingredient/kg bw, respectively), a further group of four fasted females was given a single oral dose of test item at a dose level of 910 mg/kg bw (equivalent to 300 mg active ingredient/kg bw). Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. The animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw) was found dead one day after dosing. There were no deaths at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw). The clinical observations noted were exophthalmos and hunched posture (at a dose of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw)). Signs of systemic toxicity noted in the initial animal treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw) were hunched posture, noisy respiration and pilo-erection. No signs of systemic toxicity were noted in the additional four animals treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw). Surviving animals showed expected gains in bodyweight. Abnormalities were noted at necropsy of the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw), that died during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study. The acute oral median lethal dose (LD50) of the test item in rat was estimated to be in the range 910-6061 mg/kg bw (equivalent to 300-2000 mg active ingredient/kg bw).