Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental Phase: 21 December 2017 to 11 January 2018. Report Issue: 28 February 2018.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
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:
solid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Wistar (RccHan:WIST)™ strain rats
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 of age
- Weight at study initiation: At east 200g. The weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study: No
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The initial two animals were housed individually throughout the study. The further group of eight animals (four male and four female) were housed individually during the 24-hour exposure period and in groups of four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back or flank
- % 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
- Time after start of exposure: 24 hours. Treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: The test item, moistened with arachis oil BP.

Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
four males and four females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and skin reactions.

Results and discussion

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 unscheduled deaths on the study.
Clinical signs:
There were no signs of systemic toxicity
Body weight:
All animals showed expected gains in body weight over the observation period except for three females who showed a body weight loss or no gain in body weight during the first week but expected gain in body weight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.
Executive summary:

 Introduction

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method used was designed to meet the requirements of OECD Guideline for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

 

Methods

Initially, two animals (one male and one female) were given a single, 24 hour, semi‑occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality: There were no deaths.

Clinical Observation: There were no signs of systemic toxicity.

Dermal Irritation: There were no signs of dermal irritation.

Body Weight: All animals showed expected gains in body weight over the observation period except for three females which showed a body weight loss or no gain in body weight during the first week but expected gain in body weight during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.