Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12-06-2014 to 13-10-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
inspected: March 2014; signature: May 2014
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: In refrigerator 4°C in the dark, under nitrogen
- Other: clear colourless

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan : WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Females (if applicable) nulliparous and non-pregnant: Yes.
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: Males: 250 - 280 g ; Females: 211 - 247 g; the weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study: Not applicable
- Housing: suspended solid floor polypropylene cages furnished with woodflakes; housed individually throughout the initial 24 exposure period and then in groups of five by sex for the remainder of the study.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: 12-06-2014 to 26-06-2014

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the day before treatment the back and flanks were clipped free of hair. Dorsal area application.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: The area of application was covered piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable.
- Constant volume or concentration used: Dose volume was ca. 2.07 mL/kg. Dose level was adjusted by bodyweight.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex per dose (5 male/5 female)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, and 4 hours and subsequently once daily for 14 days. Local effects were examined once daily for 14 days after the completion of the 24-hour exposure period. Full details on the scoring and criteria (consistent with Draize) are given in the full study report. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
No statistical analyses were performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
- Clinical observations: No signs of systemic toxicity were noted during the observation period.
- Dermal reactions: No dermal reactions were noted during the study.
Body weight:
Animals showed expected gains in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Organ weights: Not reported.
- Histopathology: Not reported. No macropathological abnormalities.
- Potential target organs: Not applicable.
- Other observations: Not applicable.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat. Under the conditions of this study and under the Globally Harmonized Classification System of Classification and Labelling of Chemicals (GHS), the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 402 and EU Method B.3 in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar strain rat. A group of ten animals (five males and five females) 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. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no signs of systemic toxicity. There was no mortality during the study. No signs of dermal irritation were noted. Animals showed expected gains in body weight during the study. There was no abnormalities on necropsy. Under the conditions of this study, the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat. Under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.