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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Test systemSpecies: Rat, Wistar HsdCpb: WU, males (m) and females (f) Breeder: F. Winkelmann, 33178 Borchen Age: approx. 6 to 8 weeksIdentification and adaptationHealthy 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 dietThe 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.

Administration / exposure

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.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, the test item 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 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, the test item 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.