Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-09-20 - 2016-10-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

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
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate issued by "The Department of Health of the Government of the United Kindom" (2016-10-28).
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMs (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: at least 200g, the weight variation did not exceed ± 20% of the mean weight for each sex.
- Housing: The animals were housed idividually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 -70%
- Air changes (per hr): at least 15 per hour
- 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: shorn skin on back and flanks of each animal
- % coverage: approximately 10% of total body surface area
- Type of wrap if used: self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Dose level: 2000 mg/kg
- Dose volume: 1.8 mL/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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 30 minutes, 1, 2 and 4 hours after exposure. On the subsequent days once daily. Weighing of the individuals occured on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: skin reactions observed daily, body weight (day 0, 7 and 14), toxicological effects, behavioural and clinical abnormalities.
Statistics:
Not reported. Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:
Not performed. Use of available information on the toxicity of the test item to determine the dose.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
Animals showed expected gain in body weight over the study period, except for two females which showed body weight loss or no gain in body weight during the first week but expected gain of body weight during the second week
Gross pathology:
Very slight erythema (barely perceptible) was observed at the test sites of all animals 1 day after dosing and persisted in one male and two females 2 days after dosing.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS (CLP) criteria not met
Conclusions:
No mortality occurred at a maximum tested level of 2000 mg/kg bw and the study has been completed as a limit test. The LD50 is considered to be more than 2000 mg/kg.
Executive summary:

An acute dermal toxicity study was conducted according to OECD Guideline 402 and in compliance with GLP criteria. The initial weight of each of 5 Wistar strain rats per sex was at least 200 g. Approximately 24 hours prior to the application of the test material, the hair of each animal was closely clipped on the back and the flanks. A single dose of 2 g/kg of the test material was administered dermally to five male and female animals. The test material was kept in contact with the skin for a period of 24 consecutive hours under a self-adhesive bandage. The application site and surrounding areas were wiped clean of residual test material at the end of the 24-hour exposure period with cotton wool moistened with distilled water. The animals were observed for abnormal clinical and behavioral signs frequently on the day of dosing and once daily for 14 days after treatment. Individual body weights were recorded on the day of dosing and on days 7 and 14. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Body weight was recorded on day 0, day 7 and on day 14: animals showed expected gain in body weight over the study period, except for two females which showed body weight loss or no gain in body weight during the first week but expected gain of body weight during the second week. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. Very slight erythema (barely perceptible) was observed at the test sites of all animals 1 day after dosing and persisted in one male and two females 2 days after dosing. There were no deaths during the study period and no signs of systemic toxicity were noted during the observation period. An acute dermal median LD50of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.