Registration Dossier

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:
other: GLP 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:
adopted Feb. 1987
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan no. 8147
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Laromer LR 8887
- Physical state: clear, yellowish liquid
- Analytical purity: 78.1 g/100 g by H-NMR spectroscopy
- Purity test date: 2011-11-03
- Lot/batch No.: 110009P040
- Expiration date of the lot/batch: no data
- Stability under test conditions: guaranteed by sponsor
- Storage condition of test material: room temperature in the dark
- Other: density as determined by Bioassay: 1.098 g/ml

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females: app. 12 weeks
- Weight at study initiation: males 228 - 237g, females: 209-211g
- Fasting period before study: no
- Housing: single in makrolon cages, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- 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
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.82ml/kg b.w.

Duration of exposure:
24h
Doses:
2000mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of exposure, at least once daily on each workday thereafter
- Frequency of weighing: shortly before administration, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin findings (30-60min after exposure, several times thereafter)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occured
Clinical signs:
no systemic clinical signs were observed. For local irritation, see table 1 (males) and table 2 (females)
Body weight:
normal increase
Gross pathology:
no abnormalities noted

Any other information on results incl. tables

Table 1:

Nature and duration of local clinical signs(males)
Dose (mg/kg bw): 2000
Sex: male
Administration: 1
No. of animals: 5
Animal No.: R 954 R 955 R 956 R 957 R 958
Abnormalities:          
Erythema grade 1: d9 - d12 d7 - d9 d13 d6 - d9 d8 - d9
Erythema grade 2: d1 - d2;
d7 - d8
d1 - d2; d6 d1 - d2;
d9 - d12
d1 - d5 d1 - d2; d7
Erythema grade 3: d5 - d6 d5 d5 - d8 - d5 - d6
Edema grade 1: - d1 - d2 d1 - d2 d1 - d2 d1 - d2
Incrustations: d5 - d8 d5 - d6 d5 - d12 - d5 - d8
Scaling: d5 - d 13 d5 - d7; d9 d5 - d14 d5 - d8 d5 - d9
Sever scaling: - d8 - - -
Skin findings beyond the
application area:
- - d6 - d13 - -
Significant scratching
behavior
d2 - d6 d2 - d5 d2 - d6 d2 - d5 d2 - d6

d: day

Table 2:

Nature and duration of local clinical signs(females)
Dose (mg/kg bw): 2000
Sex: female
Administration: 1
No. of animals: 5
Animal No.: R 959 R 960 R 961 R 962 R 963
Abnormalities:          
Erythema grade 1: d12 - d13 d14 d12 - d13 d12 - d13 d14
Erythema grade 2: d1 - d2;
d8 - d9
d1 - d2;
d12 - d13
d1 - d2;
d7 - d9
d1 - d2 d1 - d2;
d12 - d13
Erythema grade 3: d5 - d7 d5 - d9 d5 - d6 d5 - d9 d5 - d9
Edema grade 1: d6 - d9 - - d6 -
Edema grade 2: - - - d5 -
Incrustations: d5 - d12 d5 - d14 d5 - d12 d5 - d14 d5 - d14
Scaling: d5 - d14 d5 - d14 d5 - d9 d5 - d14 d5 - d14
Skin findings beyond the
application area:
- d6 - d14 d6 - d9 d6 - d14 d6 - d14
Significant scratching
behavior
d1 - d5 d1 - d5 d2 d2 - d3 d1 - d5

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test material after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. The following test item-related local effects were recorded during the course of the study:

· No mortality occurred

· No signs of systemic toxicity were observed in the animals

· Slight to moderate erythema (grade 1 to 3)

· Slight to well-defined edema (grade 1 to 2)

· Incrustations

· Scaling

· Severe scaling

· Skin findings beyond the application area

· Significant scratching behavior

· The mean body weight of the animals increased within the normal range throughout the study period

· No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.