Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
84/449/EEC
GLP compliance:
yes
Test type:
standard acute method
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 ANIMALS
- Strain specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG, Kastengrund, SPF-breed
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: male 197 g - 213 g, female 194 g - 206 g on day 1 (treatment)
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Albtromin 1324)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: none, because bread under identical conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 0.5 g test substance + 0.5 ml physiolog. saline
- For solids, paste formed: yes
- prepared paste was arranged on 6 cm x 8 cm aluminium foil
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
TEST SITE
- approximately 30 cm2 of the back were shaved; prepared test substance paste on aluminium foil was placed on the dorsal skin and fixed
- Area of exposure: approximately 6 cm x 8 cm;
- Type of wrap if used: surgical gauze patch (Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 24 hours

- Duration of observation period following administration: 14 days starting with treatment day 0
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes and approximately 1, 2, 4 and 6 h after administration on day 0 and twice daily on days 1-14
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 6 h after administration on day 0 and twice daily on days 1-14
body weights: on days 0 (prior to administration), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths
Clinical signs:
none
Body weight:
male: average increase of body weight 44 %
female: average increase of body weight 9,6 %
Gross pathology:
No macroscopic findings at scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
67/548/EEC: Acute dermal toxicity: no classification warranted
1272/2008/EC: Acute dermal toxicity: no classification warranted
Executive summary:

One group of five male HoeWISK (SPF71) rats and one group of five female HoeWISK (SPF71) rats were treated with the test item by dermal route administration at a dosage of 2000 mg/kg body weight. 0.5 g the test item was pasted in 0.5 ml vehicle (pyhsiolog. saline) .

The animals were examined twice daily during and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 4 and 6 hours after treatment on day 0 and once daily during test days 1 -14. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 4 and 6 hours after administration on test day 0 (with the clinical signs) and daily during days 1 -14. Body weights were recorded on day 0 (prior to administration) and on days 7 and 14. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No macroscopic findings were recorded for the animals at scheduled necropsy.

The median lethal dose of the test item after single dermal administration to male and female rats, observed over a period of 14 days is:

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