Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 15 november 2000 and 14 December 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Releability 1

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
before 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
-
Specific details on test material used for the study:
Test material information:
2-(2-undecyl-4,5-dihydro-1H-imidazol-1-yl)ethanol
Specific details on test material used for the study:
name: Lauryl-hydroxyethylthylimidazoline
CAS-Number: 136-99-2
Content >85%
Appearance: white solid
Storage conditions: darkness at approximately 20°C In a fume
Impurities (identity and concentrations):
Composition of test material, percentage of components: >85%
Lot/batch No.: Batch 1
Expiration date of the lot/batch: August 29, 2002
Stability and homogeneneity in the vehicle: is guaranteed for 1 hour

Test animals

Species:
other: Rat common species
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Rat
Species: Sprague-Dawley
Strain: HSD: Sprague-Dawley SD
Origin HARLAN WINKELMANN Gartenstr. 27, 33178 Borchen
SPF breeding colony
- Source:
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 6-10 weeks
-Randomization: Randomization schemes 2000.0412, 2000.0413, 2000.0571.2000.0572
-Animal maintenance: In fully air conditionned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Weight at study initiation: male animals: mean= 195 g(=100%)
S=±6.5g
min=185 g 8-5.1%)
max=205g(+5.1%)
n=10
female animals: mean=182g (=100%)
S=±5.5 g
min=174g(-4.4%)
max=190g(+4.4%)
n=15
-Food: Ssniff® R/M-H (V1534), ad libitum
-Withdrawal of food: from about 16 hours before to 3-4 hours after treatment
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
Animal identification: fur marking with KMn04 and cage numbering.
- Acclimation period: at least 7 daya

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): relative Humidity: 50±20%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours daily

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
Preparation of the testb compound was emulsified in the statd concentrations In sesame oil and distributed homogeneously by means of a magnetic stirrer. The stability and the homogenity of the test substance in the vehicle was determined by analytical methods.
Doses:
315,500 and 2000 mg/kg b.w.
No. of animals per sex per dose:
5 animals per sex per dose (315 and 2000mg/kg b.w.)
5 females (500 mg/kg b.w.)
Control animals:
no
Details on study design:
The test substance preparations were administrated by gavage to fasted animals at the stated dosage. The observation periode following treatment lasted for 14 days. Symptoms and lethality were recorded twice every day ( in the morning and in the afternoon). On weekends and public holidays only once. Animlas found dead were dissected as soon as possible and examined for macroscopically visible changes. During this time the animals were weight weekly. At the end of the observation period surviving animals were killed by carbon dioxide asphyxiation dissedsd and also examined for macroscopically visible changes.
Statistics:
The LDso, the 95 % limits of confidence and the equation of the probitline were established in female
animals on the basis of the lethality rates by probit analysis.
(method of FIELLER and SIDAK, programs supplied by IS Research, Aventis Pharma Deutschland
GmbH).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
448.9 mg/kg bw
Based on:
test mat.
Mortality:
Please see "any other information section"
Clinical signs:
The following clinical signs were observed after the administration of the test material:
- hypoactivity, stupor, squatting posture, stilted, uncoordinated and ataxic gait, irregular respiration,
painting, gasping, respiratory sounds, drawn in flanks,
bristling coat, narrow palpebral fissures and trembling.
Body weight:
Development of bodyweight was not impaired.
Gross pathology:
Macroscopic examination of the animals found dead revealed the following findings:
Black discolored spleen, stomach filled with gas, diffuse reddening of the stomach mucosa and deta
chment of the stomach and small intestine mucosa as well as blood in the small intestine, small int
estine filled with dark yellow mucous, urine bladder filled with dark red fluid, positive test of blood in u
rine, abdominal cavity filled with light red fluid.
The animals killed at the end of the observation period showed no macroscopically visible changes.

Any other information on results incl. tables

Under the conditions described above, the following lethality rates were observed:

 Dose (mg/kg b.w.)  Male animals Female animals
 Absolute  Relative (%) Absolute          Relative (%)
 2000 5/5  100  5/5  100
 500  - -  3/5  60
 315  0/5  0  1/5  20

Applicant's summary and conclusion

Executive summary:

The acute oral toxicity testing of Lauryl-hydroxyethylimidazolinei n the rat yielded the following median lethal dose (LD50): Female animals: 448.9 mg/kg body weight Male animals did not show a higher sensitivity to the test substance. Lethality occurred up to day two of the study. Besides unspecific symptoms the animals showed impairments of motility and respiration as well as drawn in flanks. Additionally, hypoactivity, stupor, bristling coat, narrow palpebral fissures and trembling and were observed. Development of body weight was not impaired. Necropsy of the decedent animals revealed black discolored spleen, stomach filled with gas, diffuse reddening of the stomach mucosa and detachment of the stomach and small intestine mucosa as well as blood in the small intestine, small intestine filled with dark yellow mucous, urine bladder filled with dark red fluid, positive test of blood in urine, abdominal cavity filled with light red fluid. The animals killed at the end of the observation period showed no macroscopically visible changes.