Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-25 to 2011-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EU Method B.3 (Acute Toxicity ((Dermal))
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:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Solid

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: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: 199-217 g (male) and 237-262 g (female)
- Housing: Makrolon cage, type III; single housing
- Diet: SDS Special Diets Services
- 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): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm² (corresponds to at least 10% of the body surface)

REMOVAL OF TEST SUBSTANCE
- Washing : Afterwards removal of the semiocclusive dressing, rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.33 mL/kg bw
- Constant volume or concentration used: 60 g/100 mL
- For solids, paste formed: yes, suspension in olive oil Ph. Eur
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male /5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each work day for the individual animals.
- Necropsy of survivors performed: yes, necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
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. For local effects, please refer to the section "Any other information on results inc. tables" below.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range, with the exception of one female which showed stagnation of body weight during the first post-exposure week, but gained weight in the second week in a 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.

Any other information on results incl. tables

Nature and duration of local clinical signs in male animals

Animal No.:

1

2

3

4

5

Erythema grade 1

d5 – d9

d5 – d6

d2 - d5

d1 - d5

d5 – d9

Erythema grade 2

d1 – d2

d1 – d2

d1

-

d1 – d2

Edema grade 1

-

-

d2

d1- d2

-

Edema grade 2

d1-d2

d1-d2

d1

-

d1 – d2

Incrustions

d5 – d9

-

-

-

d5- d8

Scaling

-

d5 – d9

-

-

d5 – d9

Nature and duration of local clinical signs in female animals

Animal No.:

1

2

3

4

5

Erythema grade 1

d1

d2

d2

d5

d5

Erythema grade 2

-

d1

d1

d2

d1 – d2

Erythema grade 3

-

-

-

d1

-

Edema grade 1

d1

d1

d1

d1

d1- d2

Scaling

-

-

-

-

d5 – d8

Local effects in male animals

In four male animals well-defined erythema (grade 2) was noted on study day 1, persisted in three of these animals until study day 2 and decreased to very slight erythema (grade 1) on study day 5. This grade persisted up to study day 6 (one animal) or 9 (two animals).

In the fourth of these animals well-defined erythema decreased to very slight and was already seen on study day 2 and persisted until study day 5 after administration. Very slight erythema was seen in the fifth male from study day 1 until study day 5. On study day 1 slight edema (grade 2) was noted in four animals and persisted in three males until day 2. In the fourth male edema decreased to very slight (grade 1) on day 2. In the fifth male very slight edema was observed from study day 1 until day 2. Furthermore incrustations and scaling were noted from study day 5 until study day 8 or 9 in two males, each.

Local effects in female animals

Very slight erythema (grade 1) was noted in one animal on study day 1, while in three others well-defined erythema (grade 2) was noted on study day 1, persisted in one of these animals until study day 2 and decreased to very slight on study day 5. In the other two females very slight erythema was noted on study day 2. Moderated erythema (grade 3) was seen in the fifth animals on study day 1, but decreased step-wise from well-defined erythema on study day 2 to very slight erythema on study day 5. Very slight edema (grade 1) was observed in all females on study day 1 and persisted in one out of these animals until day 2. Furthermore scaling was noted in one female animal from study day 5 until study day 8.

Applicant's summary and conclusion