Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Oct 16 - Oct 30 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed in compliance with the Good Laboratory Practice (GLP) regulations (revised in 1997, ENV/MC/CHEM(98)17). The method followed that described in the OECD Guidelines for Testing of Chemicals (Adopted: 4 April 1984) No 423 "Acute Oral Toxicity – Acute Toxic Class Method".

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Batch: E96844401
Purity: 99.6 % (HPLC)
Designation: 272101
Specification: Liquid Crystal
Analytical report: Merck KGaA Darmstadt, Dr. Götzmann
End of release: Jun 30, 1998
The test material was freshly prepared with liquid paraffin prior to administration.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Test system
Species: Rat, Wistar HsdCpb: WU, males (m) and females (f)
Breeder: F. Winkelmann, 33178 Borchen
Age: approx. 7 to 9 weeks
Mean initial weight: 170 (161-182) g

-Identification and adaptation
Healthy young animals were allocated to the study group at least 7 days before dosing to allow for acclimatization.
The rats were identified by an ear tattoo.

- Housing and diet
The rats were housed in an air-conditioned room of about 25 m^2 in the Institute of Toxicology. Lighting was controlled by a timer to provide a 12 hour light - 12 hour dark regime.

The rats were kept separately in type III Makrolon cages with a shelter, placed on mobile racks. Conventional softwood granulate was used
as the bedding. One day before treatment, and up to 24 hours after dosing, metal grids were placed above the softwood granulate.
The cages and the metal grids had been machine-cleaned before the start of the experimental part. The bedding was changed two times per
week.

Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 21 to 24 °C
and the relative atmospheric humidity 45 to 75 %.

Diet was withheld from 17 hours before until up to 4 hours after treatment. At all other times food and tap water from Makrolon drinking
bottles were available to the rats ad libitum.

According to the specifications given by the manufacturer, the diet, Provimi Kliba 3433.0, had been checked by independent laboratories.
Analysis included qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
The drinking water was periodically analyzed according to the German regulations for human drinking water.

The softwood granulate was analytically checked by independent laboratories.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
The rats received the test material preparation orally by means of a stomach tube.
Doses:
2000 mg/kg bw (limit test)
100 g/L, 20 mL/kg
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
-- Observation for clinical symptoms
The behavior and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily.

-- Body weight
All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.

-- Pathology
All rats were sacrificed at the end of the experimental part by C02-asphyxia and subjected to gross pathological investigations.

-- Archive statement
All raw data, specimens, and the final report are stored in the archives of the Merck KGaA Institute of Toxicology.
Statistics:
The body weight data were processed by means of a PC - program, developed by the Institute of Toxicology of Merck KGaA, Darmstadt.
The body weight development of each rat and group was determined. The group mean value and the difference to the first value, expressed as percentage, were calculated for each measurement and printed out on tables.

Results and discussion

Preliminary study:
Only wet anal region was observed on day one after treatment. Thus the study was performed as limit test.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000
Mortality:
No mortality observed. All rats survived the observation period.
Clinical signs:
Only wet anal region was observed on day one after treatment. No further signs of toxicity were detected in the 5 male and 5 female rats after treatment with 2000 mg/kg of CC-5-V.
Body weight:
Body weight development of the treated rats was normal.
Gross pathology:
At necropsy no organ alterations were seen.
Other findings:
None

Any other information on results incl. tables

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in man.

Study design

The test material CC-5 -V was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. Directly before the administration the test material was prepared with liquid paraffin as vehicle. This study was performed at a fixed dose of 2000 mg/kg bw (limit test).

Results

Only wet anal region was observed on day one after treatment. No further signs of toxicity were detected in the 5 male and 5 female rats after treatment with 2000 mg/kg bw of CC-5 -V. All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

Conclusions

According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the result of this study, it is concluded, that CC-5-V has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw following oral treatment in rats. According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg.
Executive summary:

The test material CC-5 -V was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight.

Directly before the administration the test material was prepared with liquid paraffin.

Only wet anal region was observed on day one after treatment. Thus the study was performed as limit test.

The gross pathological examination revealed no organ alterations.

For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg.