Registration Dossier

Administrative data

Description of key information

With the test material CCP-V-1, one oral and one dermal acute toxicity study were conducted. Both studies showed no mortality, no body weight change and no signs of toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 24 - June 08, 2000
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".
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
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 information:
Composition 1
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. 6 to 8 weeks

- Identification and adaptation
Healthy young animals were allocated to the study group at least 7 days before dosing to allow for acclimatization.

- Housing and diet
The rats were housed in an air-conditioned room. 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.

Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 20 to 22 °C
and the relative atmospheric humidity 51 to 80 %.

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.

The diet (LONG LIFE for mice and rats 9439, Eberle Nafag) is checked by independent laboratories by an independent laboratory approved by the Geman government. 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.

Route of administration:
oral: gavage
Vehicle:
other: Methocel K4M Premium
Details on oral exposure:
The rats received the test material preparations orally by means of a stomach tube.
Doses:
The test material concentration was 100 g/L.
The dose was 20 mL/kg or 2000 mg/kg bw.
No. of animals per sex per dose:
3 (m) / 3 (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.
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000
Mortality:
No mortality observed. All rats survived the observation period.
Clinical signs:
No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg of CCP-V-1.
Body weight:
Body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy no organ alterations were seen.
Other findings:
None

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw of CCP-V-1.

All rats survived the observation period. Body weight development of the treated rats was inconspicuous. At necropsy no organ alterations were seen.

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 CCP-V-1 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:

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 CCP-V-1 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 aqueous Methocel K4M Premium solution as vehicle.

This study was performed according to the ,,Acute toxic class method" (ATC).

Results

No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died.

The gross pathological examination revealed no organ alterations.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Reliability Score 1 (guideline compliant GLP study)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to Good Laboratory Practice (GLP) and followed the OECD Guideline for Testing of Chemicals, No. 402 and according to Commission Directive 92/69/EEC.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
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. 6 to 8 weeks

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. 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.

Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 22 to 23 °C
and the relative atmospheric humidity 46 to 72 %.

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.

The diet, Provimi Kliba 3433.0, had been checked, according to the specifications of the manufacturer 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.

Type of coverage:
occlusive
Vehicle:
other: aqua pro injectione
Details on dermal exposure:
The backs and abdomens of the rats were shaved with an electric hair clipper not later than one hour before treatment.
The test material was prepared, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
-- Observation for clinical symptoms
On the day of treatment the general condition and motility of the rats were slightly affected by the tape. It was difficult to distinguish between slight clinical findings and reactions due to fixation by the tape. The behavior and general condition of all rats were monitored for at least 6 hours after 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. They were subjected to a gross pathological investigation.

-- Statistics and evaluation
The body weight data were recorded with a PC-program. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All rats survived the observation period. The lethal dose was regarded to be > 2000 mg/kg.
Clinical signs:
No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg bw.
Body weight:
The body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy, no organ alterations were seen.
Other findings:
None
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the result of this study, CCP-V-1 can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.
Executive summary:

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 dermal toxicity of the test item in man.

Study design

The test material CCP-V-1 was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration the test material was moistened with aqua pro injectione, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf), The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.

Results

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.

Conclusions

Based on the result of this study, CCP-V-1 can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Reliability Score 1 (guideline compliant GLP study)

Additional information

Oral route of administration

CCP-V-1 was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. This study was performed according to the "Acute toxic class method" (ATC).

No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations.

Dermal route of administration

CCP-V-1 was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight.

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous.The gross pathological examination revealed no organ alterations.

Based on the result of this study, CCP-V-1 can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Summary

Based on the results of these studies, CCP-V-1 has no acute toxic potential with LD50 values higher than 2000 mg/kg after oral and dermal application to rats.


Justification for selection of acute toxicity – oral endpoint
Guideline compliant GLP study

Justification for selection of acute toxicity – dermal endpoint
Guideline compliant GLP study

Justification for classification or non-classification

Based on the results for acute oral and dermal toxicity in rats, CCP-V-1 is considered to have no acute toxic potential. The expected LD50 values are higher than 2000 mg/kg bw after oral and after dermal administration to rats.Therefore, CCP-V-1 is not classified according to EU Directive 67/548/EC amended and repealed by EU Regulation No.1272/2008 and CLP.