Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April to June 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail. Test procedure is comparable to guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
not specified
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:
TNO/W 74
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier.
- Females (if applicable) nulliparous and non-pregnant: Not specified.
- Age at study initiation: not specified.
- Weight at study initiation: 150 – 200 g.
- Fasting period before study: 16 h.
- Housing: during acclimation and observation period: Makrolon Type III/II cages.
- Diet (e.g. ad libitum): Altromin-R rat and mouse maintenance diet, ad libitum.
- Water (e.g. ad libitum): Water, ad libitum.
- Acclimation period: not specified; study reports that animals were handled "soberly" (implies carefully/gently).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified.
- Humidity (%): Not specified.
- Air changes (per hr): Not specified.
- Photoperiod: Not specified.

IN-LIFE DATES: From: April 1980 To: June 1980.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
poloxamer
Remarks:
reported under an alternative trade name ("Lutrol").
Details on dermal exposure:
TEST SITE
- Area of exposure: previously-clipped and undamaged back skin.
- % coverage: Not specified.
- 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 flushed with water, soap and cotton wool.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
- Concentration (if solution): Not specified.
- Constant volume or concentration used: A solution of the test item in lutrol was used, in sufficient quantity to deliver a dose of 5000 mg/kg bw test-item.
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 per sex per dose (5 male/5 female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted during the acclimatisation period, and throughout test day 1; Subsequent observations occured daily for days 2 to 15. Body weights were measured prior to testing, but not reported. Local effects were examined daily days 2 to 15 after the completion of the 24-hour exposure period. The study report does not disclose observations of erythema, however elsewhere in the report a separate skin-irritation/corrosion test is performed and documented.
- Necropsy of survivors performed: yes
Statistics:
Where necessary, LD50/LC50 calculations and confidence-interval calculations were performed using "Probit-Analyse" (Fink and Hund, Arzneimittelforschung 15, 624, 1965).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
- Clinical observations: None reported.
- Dermal reactions: Not reported; however a separate skin irritation/corrosion study elsewhere in the study report covers this.
Body weight:
No remarks were made regarding bodyweight; applicant assessment indicates that based on the rest of the study report (where bodyweights are reported), this implies that animals showed expected gains in bodyweight.
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.

Any other information on results incl. tables

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 5000 mg/kg bw in male/female Wistar rats. Applicant assessment indicates 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 on the basis of absence of significant clinical toxicological effects and/or bodyweight increases in all males/females.
Executive summary:

The study was performed historically according to a method similar to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal), to assess the acute dermal toxicity of the test item in the TNO/W 74 strain rat. A group of ten animals (five males and five females) was given a single, 24 hour semi-occluded dermal application of the test item delivered in poloxamer to intact skin at a dose level of 5000 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. Applicant assessment indicates there were no toxicologically significant effects on bodyweight. Signs of dermal irritation were not reported; however an additional study in the same report documents a skin-irritation/corrosion test. The dermal LD50 was established to exceed 5000 mg/kg bw in male/female TNO/W 74 rats. Applicant assessment indicates 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 on the basis of absence of significant clinical toxicological effects and/or bodyweight increases in all males/females.