Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date: 24 January 2018 Experimental completion date: 14 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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guideline for the Testing of Chemicals No. 402 “Acute Dermal Toxicity: Fixed Dose Procedure” (adopted 09 October 2017)
Deviations:
yes
Remarks:
Please refer to the materials and methods section.
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Identification: Fatty acids, C18-unsatd., dimers, polymers with epichlorohydrin
Batch: 52611021
CAS Number: 68475-94-5
EC Number: 500-215-4
Purity: 95-100%
Physical state / Appearance: Clear yellow liquid
Expiry Date: 01 December 2018
Storage Conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Three female Wistar (RccHan:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200 g, and were 8 to 12 weeks of age. The weight variation did not exceed ±20% of any previously treated animals.

Animal Care and Husbandry
The animals were individually housed throughout the study in suspended solid floor polypropylene cages furnished with wood flakes. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 degreesC and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
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.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
On the day before treatment the back and flanks of each animal were clipped free of hair. The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. Shortly after dosing the dressings were examined to ensure that they were securely in place.

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 arachis oil BP to remove any residual test item.


Duration of exposure:
24 hours
Doses:
2000mg/kg/bodyweight
No. of animals per sex per dose:
Three females were treated with the test item at a dose level of 2000 mg/kg body weight
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
-The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2, 4 and 6 hours after dosing and subsequently once daily for 14 days. Due to a technician error, the Day 8 observations (clinical and dermal) for animals 2-0 and 2-1 were not performed. This was considered not to affect the purpose or integrity of the study as no evidence of dermal irritation or signs of toxicity were observed throughout the observation period pre or post Day 8.
After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation.

Results and discussion

Effect levels
Key result
Sex:
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:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No signs of dermal irritation were noted during the observation period.

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 female 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.

Methods

Initially, 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 2000 mg/kg body weight. Based on the results of the initial test, a further two female animals were 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 Observations. 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.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

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