Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05-09-2001 to 25-10-2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

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: February 2000 ; signature: April 2000
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: At room temperature under nitrogen in the dark.
- Other: Clear colourless

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl: CD (SD) IGS BR
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: ca. 8 weeks age (nulliparous and non-pregnant)
- Weight at study initiation: > 200 g (actual: 212 – 238 g males and 207 – 224 g females)
- Fasting period before study: Not applicable
- Housing: during acclimation: group housed by sex; during study: individually housed in polypropylene cages furnished with softwood bedding.
- 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 to 25 °C (or 22 ± 3 °C)
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 05-09-2001 to 19-09-2001

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 by a semi-occlusive dressing and wrapped with a piece of elastic self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water 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 (or dose volume 2.19 mL/kg)
- Concentration (if solution): See below.
- Constant volume or concentration used: 2.19 mL volume ; at a dose level of 2000 mg/kg bw test item.
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 days 2 to 15. Local effects were examined once daily days 2 to 15 after the completion of the 24-hour exposure period. Full details on the scoring and criteria (appears consistent with Draize for Erythema) 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: All sites indicated no irritation (score = 0) from day 1 to day 14. There was evidence of crust formation on days 4 to 5 in female-1. This observation ceased on day 6.
Body weight:
It was considered there was no toxicologically significant effects on bodyweight. All males/females gained bodyweight 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 Sprague-Dawley 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 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test item in the Sprague-Dawley Crl: CD (SD) IGS BR 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 was no mortality during the study. There were no signs of system toxicity or abnormalities on necropsy. It was considered there was no toxicologically significant effects on bodyweight. All males/females gained bodyweight during the study. No signs of dermal irritation were noted (score 0) up to day 14 in all males/females. Crust formation was observed in days 4 and 5 on one female application site only which reversed at day 6. The dermal LD50 was established to exceed 2000 mg/kg bw in male/female Sprague-Dawley Crl: CD (SD) IGS BR 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.