Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 25, 2014 - December 18, 2014
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Solid / yellow
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean weights males: 230 g; mean weights females: 209 g
- Fasting period before study: no
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity (%): 30 – 70
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: 0.5% solution of CMC (sodium carboxymethylcellulose) in deionized water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used:

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.00 g/kg bw
- Concentration: 40g/100ml (paste)
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24h
Doses:
2000 mg/kg body weight
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: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
No systemic clinical signs were observed during clinical examination. Due to the yellowish discoloration of the application area no local findings such as erythema could be determined in all animals on study day 1. Thereafter, no erythema or edema were observed, however slight yellowish discoloration of the application area was still present in all animals until study day 3.
Body weight:
The mean body weight of all animals increased within the normal range throughout the study period with one exception in the female group. The body weight increased in this animal within the normal range during the first week, but stagnated during the second week. As this female did not show any symptoms or change in behavior, the observed stagnation is considered to be unspecific.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 test material (as a suspension in 0.5 % CMC-solution) 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 mortality occurred signs of systemic toxicity were observed. Due to the yellowish discoloration of the application area no erythema could be determined on study day 1 only. Slight yellowish discoloration of the application area was observed on the first three days after application. The mean body weight of all animals increased within the normal range throughout the study period with one exception in the female group. The body weight increased in this animal within the normal range during the first week, but stagnated during the second week. As this female did not show any symptoms or change in behavior, the observed stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg body weight.