Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 September 2011 to 18 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Batch identification: 110007P040

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: males: 8 weeks, females: 12 weeks
- Weight at study initiation: 212 ± 7.05g (males); 218.4 ± 4.39 g (females)
- Fasting period before study: no
- Housing: single in Makrolon type III cages
- Diet: VRF1(P); SDS Special diets services, Altrip, Germany, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12h / 12h

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (correspond to at least 10 % of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze and stretch bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24h (directly after removal of the semiocclusive dressing)

TEST MATERIAL
- Amount applied: 1.89 mL/kg bw
- Concentration: undiluted
- Constant volume or concentration used: yes


Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
> clinical signs: several times during exposure, daily thereafter,
> body weight: day 0, weekly thereafter and on the last day of observation,
> skin findings: 30-60 min after removal of the dressing, weekly thereafter according to Draize

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:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.

local irritation (erythema up to grade 3, edema up to grade 1) were observed up to day 6 in males and up to day 10 in females. Scaling and incrustations were also observed in 1 and 2 females, respectively.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
- Local effects:
In one female animal well-defined erythema (grade 2) was observed from study day 1 until study day 3. In two females moderate erythema (grade 3) was noted from study day 1 until study day 3. In one of these two animals moderate erythema decreased to very slight erythema (grade 1) on study day 6. In the other animal moderate erythema decreased step-wise from well-defined (study day 6) to very slight erythema (study days 7 and 8).
Furthermore following findings were observed in this animal: very slight edema (grade 1) from study day 1 until study day 3, scaling on study day 6 and 7, findings beyond the application area from study day 2 until study day 7 and incrustations from study day 6 until study day 9.
In two further animals well-defined erythema (grade 2) was noticed on study day 1, but increased to moderate erythema (grade 3) and was observed on study day 2 and 3. This grade decreased step-wise: well-defined erythema was observed on study day 6, while very slight erythema was noticed on study day 7. In one of these two animals incrustations were observed from study day 6 until study day 8. All local effects were reversible until day 10 at the latest.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met