Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 May 2018 - 24 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
2017
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: 209 g
- Fasting period before study:
- Housing: individually throughout the study in suspended solid floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet , ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- After the 24 Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with dimethyl sulfoxide followed by distilled water to remove any residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1000 mg/kg bw, corresponding to 0.96 mL/kg bw
- Concentration (if solution): neat substance

Duration of exposure:
24 h
Doses:
1000 mg/kg bw
No. of animals per sex per dose:
1 female
Control animals:
no
Details on study design:
The animal was observed for deaths or overt signs of toxicity 30 minutes, 1, 2, 4 and 6 hours after dosing and on Day 1. After removal of the dressings the test sites were examined for evidence of primary irritation.
The animal was humanely killed by cervical dislocation on Day 1. The animal was subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities and examination of the sub-cutaneous layer below the treatment site. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Remarks on result:
not determinable
Remarks:
The dermal LD50 of the test item could not be accurately evaluated due to the corrosive nature of the test item.
Mortality:
The animal was killed for humane reasons due to due to the corrosive nature of the test item in accordance with the severity limit set forth in the UK Home Office Project License.
Clinical signs:
Clinical signs noted one day after dosing were hunched posture, lethargy and tiptoe gait. It was considered that these signs may have been due to the dermal reactions causing uncomfortable movement as opposed to systemic toxicity.
Body weight:
The animal lost weight over the study period.
Gross pathology:
Full thickness necrosis and hemorrhage of the underlining tissues were noted at the visual inspection of the sub-cutaneous layer at the treatment site.
Other findings:
Dark green dermal necrosis over the majority of the treatment site was surrounded by a margin of blanching and moderate erythema.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
The acute dermal median lethal dose (LD50) of CGE-PMDA adduct could not be accurately evaluated due to the corrosive nature of the test item.
Executive summary:

This study was performed to assess the acute dermal toxicity of CGE-PMDA adduct in the Wistar strain rat in accordance with OECD Guideline 402 (2017).

One female animal was given a single, 24-hour, semi‑occluded dermal application of the undiluted test item to intact skin at a dose level of 1000 mg/kg body weight. Based on the results of the initial animal, no further animals were treated. Clinical signs and body weight development were monitored during the study. The animal was subjected to gross necropsy.

The animal was killed for humane reasons due to due to the corrosive nature of the test item in accordance with the severity limit set forth in the UK Home Office Project License.

Clinical signs noted one day after dosing were hunched posture, lethargy and tiptoe gait.

Dark green dermal necrosis over the majority of the treatment site surrounded by a margin of blanching and moderate erythema was noted one day after dosing.

The animal lost weight over the study period.

Full thickness necrosis and hemorrhage of the underlining tissues were noted at the visual inspection of the sub-cutaneous layer at the treatment site. 

The acute dermal median lethal dose (LD50) of the test item in the female Wistar strain rat could not be accurately evaluated due to the corrosive nature of the test item.