Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well performed OECD study with GLP

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: Amino-C-Dion trocken
CAS No.: 69904-10-5
Purity: 93.8% (w/w)
Correction Factor: 1.0
Stability of Test Item Formulation: > 3 days at room temperature
Storage Conditions: At room temperature (range of 20 ± 5 °C, provided by Harlan Laboratories), light protected.
Safety Precautions: Routine hygienic procedures (gloves, goggles, face mask).

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Animals: Rat, RccHan: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
Number of Animals: 6 females, two groups of three females were used.
Age / Body Weight Range (when treated): 10 weeks / 177.9 g – 189.2 g
Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: At least five days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Conditions:
Standard laboratory conditions. The animal room was air-conditioned with 10 - 15 air changes per hour. The air was continuously monitored for temperature and relative humidity. The ranges for room temperature and relative humidity were 22 ± 3 °C and 30 - 70%, respectively, although the upper range for humidity were occasionally exceeded during room cleaning. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
Accommodation:
In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland), including paper enrichment (batch no. 75, Enviro-dri from Lillico Biotechnology, Surrey / UK).
Diet: Pelleted Teklad Rat-Mouse Diet 2914C (batch no. 12/11, provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum (except for the overnight fasting period prior to treatment and approximately 3 hours post dose). Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
Water: Community tap water from Itingen ad libitum in water bottles. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Test item administration:
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 17 hours (free access to water was permitted). Food was provided again approximately 3 hours after dosing. Application volume was 10 mL/kg body weight. Rationale: Oral administration was considered to be an appropriate application method as it is a possible route of human exposure during manufacture, handling and use of the test item.
Doses:
2000 mg/kg formulated at 200 mg/mL at a dose volume of 10 mL/kg.
No. of animals per sex per dose:
3 animals per dose, 2 dose groups.
Control animals:
no
Details on study design:
The observations listed below were recorded. For each group, the day of treatment was named test day 1 and counting was continued for the subsequent days of observation:
Viability / Mortality: Daily during acclimatization; prior to treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs); twice daily during test days 2-15.
Clinical Signs: Daily during acclimatization; prior to treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1; once daily during test days 2-15.
Body Weights: On test day 1 (prior to treatment), 8 and 15.
Necropsy: All animals were sacrificed by carbon dioxide asphyxiation. An external examination and opening of the abdominal and thoracic cavities for examination of major organs was performed. All macroscopic abnormalities were recorded. Thereafter, the animals were discarded. No organs or tissues were retained. Animals that died spontaneously during the observation period were examined as soon as they are found dead.

Statistics:
None recorded.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occurred during the course of the study.
Clinical signs:
Slightly ruffled fur was observed in all animals after treatment on test day 1 No clinical signs were observed in any animal from test day 2 until the end of the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age. No test item-related effect on body weight development was observed.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of Amino-C-Dion trocken after single oral administration to female rats, observed over a period of 14 days, is:
LD50 (female rat): greater than 2000 mg/kg body weight
LD50 cut-off (female rat): unclassified
Executive summary:

Two groups, of three female RccHan:WIST (SPF) rats each, were treated withAmino-C-Dion trocken by single oral gavage administration at a dose of 2000 mg/kg body weight. The test item was formulated in purified water at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

 

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2-15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during test days 2-15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15.All animals were necropsied and macroscopically examined.

 

No intercurrent deaths occurred during the course of the study.

 

Slightly ruffled fur was observed in all animals after treatment on test day 1. No clinical signs were observed in any animal from test day 2 until the end of the observation period.

 

The body weight of the animals was within the range commonly recorded for this strain and age.

 

No abnormal macroscopic findings were recorded at necropsy.

 

The median lethal dose ofAmino-C-Dion trockenafter single oral administration to female rats, observed over a period of 14 days, is:

 

LD50(female rat): greater than 2000 mg/kg body weight

LD50cut-off (female rat): unclassified