Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 February 2017 to 07 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

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)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Appearance/physical state: Light brown, slightly viscous, liquid
- Storage conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
ANIMAL INFORMATION
- Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK.
- On receipt the animals were randomly allocated to cages.
- Female rats were nulliparous and non-pregnant.
- After an acclimatisation period of at least five 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 the mean weight for each sex.

ANIMAL CARE AND HUSBANDRY
- Animals were housed in suspended solid floor polypropylene cages furnished with woodflakes.
- The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories Ltd, Oxon, UK) was allowed throughout the study.
- Diet, drinking water and bedding were routinely analysed and were not considered to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively.
- Rate of air exchange was at least 15 changes per hour.
- 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 not considered 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:
EXPOSURE TO TEST ITEM
- On the day before treatment the back and flanks of each animal were clipped free of hair.
- Using available information on the toxicity of the test item, a single group of five male and five female animals was treated with the test item at a dose level of 3390 mg/kg (specific gravity 1.128; dose volume 3.01 mL/kg).
- 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.
- Animals were caged individually for the 24-hour exposure period.
- Shortly after dosing the dressings were examined to ensure that they were securely in place.
- After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair were wiped with cotton wool moistened with distilled water to remove any residual test item.
- The animals were returned to group housing for the remainder of the study period.
- The animals were observed for deaths or overt signs of toxicity at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- After removal of the dressings, and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the scale below.
- Any other skin reactions, if present, were also recorded.
Duration of exposure:
24 hours
Doses:
Single dose of 3390 mg/kg bw (equivalent to 2000 mg/kg bw active ingredient)
No. of animals per sex per dose:
Five males and five females
Control animals:
no
Details on study design:
STUDY DESIGN
- Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

MAJOR COMPUTERISED SYSTEMS
- Delta Controls: ORCA view
Statistics:
DATA EVALUATION
- Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.
- Using the mortality data from the study, an estimate of the acute dermal median lethal dose (LD50) was made for the test item.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: equivalent to > 3390 mg/kg bw test item
Mortality:
- Individual mortality data are given in Appendix 1 (attached).
- No unplanned animal deaths took place during the study.
Clinical signs:
- Individual clinical observations are given in Appendix 1 (attached).
- No signs of systemic toxicity were noted during the observation period.
Body weight:
- Individual body weights and body weight changes are given in Appendix 4 (attached).
- All animals showed expected gains in body weight over the observation period.
Gross pathology:
- Individual necropsy findings are given in Appendix 5 (attached).
- No abnormalities were noted at necropsy.
Other findings:
- Individual dermal reactions are given in Appendices 2 and 3 (attached).
- 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 > 3390 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).
Executive summary:

GUIDELINE

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat in compliance with the OECD Guideline for the Testing of Chemicals No 402 “Acute Dermal Toxicity” (adopted 24 February 1987) and Method B.3 Acute Toxicity (Dermal) of Commission Regulation (EC) No 440/2008.

 

METHODS

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 3390 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

 

RESULTS

No animal deaths took place during the study and there were no signs of systemic toxicity or dermal irritation reported. All animals showed expected gains in body weight and 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 > 3390 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).