Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10/2011
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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Laromer LR8869
- Physical state: Liquid / colorless, clear
- Analytical purity: for details see analytical report no. 11L00263
- Purity test date: 2012-01-11
- Lot/batch No.: 110009P040
- Stability under test conditions: guaranteed by the sponsor
- Storage condition of test material: Room temperature; avoid temperatures > 25 °C; under light exclusion

Test animals

Species:
rat
Strain:
other: Wistar / Crl:WI (Han)
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: 242-296g, females: 204-220g
- Fasting period before study: no
- Housing: single in Makrolon cage, 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: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 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 (corresponds to at least 10% of body surface)
- fur clipped: 24h prior to application (dorsal and dorsolateral parts of the trunk)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze) and stretch bandage (Fixomull® Stretch)

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.86ml/kg b.w.
- Concentration (if solution): undiluted

Duration of exposure:
24h
Doses:
2000mg/kg b.w.
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 and weighing:
observations: several times on the day of application, at least once daily thereafter on each workday
skin findings: 30-60 minutes after removal of the semi-occlusive dressing, several times until last day of observation
body weight: on day 0 prior to application, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology, local skin reactions

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortatlity
Mortality:
no
Clinical signs:
male and female: no systemic effects
male - local effects:
In three males slight erythema (grade 1) was observed on study day 1 and 2. Well-defined erythema (grade 2) was observed in the two other animals on study day 1 and 2 after application. In these two animals slight edema (grade 1) was observed on study day 1 only.
female - local effects:
In three females slight erythema (grade 1) was observed on study day 1 which increased to well-defined erythema (grade 2) on study day 2. In one of these animals this grade was noted until study day 5 but decreased again to slight (grade 1) on study day 6. Additionally incrustations were observed in this animal from study day 5 until study day 7. In one animal well-defined erythema was observed from study day 1 until study day 6 which decreased to slight erythema on study day 7 and persisted until study day 9 after application. Slight edema (grade 1) was observed in this female animal from study day 1 until study day 5. In addition, incrustations (from study day 2) and scaling (from study day 5) were noted until study day 9 in this animal. Well-defined erythema was observed in the fifth animal on study day 1 and 2 after application. In this animal slight edema (grade 1) was observed on study day 1.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
no findings

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 substance 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 the 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.

· No signs of systemic toxicity were observed in the animals.

· The following test item-related local effects were recorded during the course of the study:

o Slight to well-defined erythema (grade 1 to 2)

o Very slight edema (grade 1)

o Incrustations

o Scaling

· The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

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