Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC directive 84/449/EEC
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Appearance: pink-coloured cream

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Strain: Crl.: (WI) BR - Wistar, white
Source: Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld
Animal identification: coloured marking; cage labelled with the following information: dosage, sex, date of study
Weight range at study initiation: m: 177 - 186 g, f: 168 - 201 g
Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
Illumination: artificial lighting (120 lux) from 7. 00 a.m. - 7.00 p.m.
Temp.: 20 ± 2 °C
Relative humidity: 50- 85 %
Measurement: with thermohygrometer twice daily

Prior to study initiation, the animals were acclimated to laboratory conditions for at least 7 days. 24 h before treatment, the fur was removed with electric clippers from an area of roughly 5 x 10 cm on the back of each animal. The skin was subsequently examined for abrasions and animals with healthy, intact skin were then coloured for individual identification.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Preparation and application of the test substance:
The test substance was administered as a 66.6 % dilution at 3 ml/kg body weight. The pH value has been adjusted to 6.8 with 25 % ammonic solution. The relative density of the applied solution was 1.002 kg/l. For practical reasons the terms ml and g are considered as identical units.
A single dermal application of the test substance was performed. The substance was held in contact with the skin with a porous gauze dressing and Elastoplast (Beiersdorf).
Duration of exposure:
The exposure period was 24 h.
Doses:
66.6 % dilution at 3 ml/kg body weight
No. of animals per sex per dose:
f males and 5 females
Control animals:
not required
Details on study design:
Range finding
A preliminary range finding test with a dose of 2000 mg/kg bw was conducted on two female rats.

Main study
Clinical observations:
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following intervals after patch removal: 10 min, 1 h, 2 h, 4 h, 24 h, and thereafter once daily up to day 14.

Skin reactions:
After patch removal, dermal irritation was evaluated once daily for 14 days according to a scheme based on Draize.

Body weights:
The body weights of all animals were recorded immediately before treatment (day 0) and surviving animals were reweighed on days 7 and 14 (termination).

Necropsy:
Animals found dead or killed in extremis were immediately necropsied. The surviving animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.

Evaluation of the data:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd edition, Cambridge, 1971.

Results and discussion

Preliminary study:
There were no deaths in the preliminary study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No animals died during the course of the main study.
Clinical signs:
Some animals showed a slight to moderate reduced activity 10 min - 4 h p.a. Otherwise, no abnormal clinical signs were observed.
A very slight till moderate erythema was observed in almost all of the animals for the entire observation period. Some animals had eschar on the skin and wrinkled skin. No signs of oedema were observed.
Body weight:
Weight gains were nonnal in all animals.
Gross pathology:
Gross pathological examinations at 14 days p. a. (terminal necropsies) revealed no test substance-dependent findings. Those macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which often occur spontaneously in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the 14 d dermal LD50 was established at >2000 mg/kg bw in male and female rats.
Executive summary:

A study was conducted to determine dermal toxicity of the test substance according to OECD Guideline 402 and EC Directive 84/449. The acute dermal toxicity of the test substance was investigated in 5 male and 5 female Wistar rats. On the basis of the range finding results, each animal was given a single dermal administration of 2000 mg/kg bw as a 66.6% dilution. The pH was adjusted to 6.8 with a 25% ammonic solution. The skin was exposed to the test substance for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 d. Clinical observations were conducted at regular intervals during the 14 d observation period. Body weights were measured on Days 0, 7 and 14. Gross pathological examinations were performed on animals at termination. No abnormal clinical signs were observed apart from a slight to moderate reduced activity in the animals. A very slight till well-defined erythema was observed in almost all of the animals for the entire observation period. Some animals had eschar on the skin and wrinkled skin 5 - 14 d post-administration (p.a.). No signs of oedema were observed. No pre-terminal deaths occurred. All animals showed normal weight gains. Gross pathological examinations at 14 d p.a. (terminal necropsy) revealed no test substance-dependent findings. Under the study conditions, the 14 d dermal LD50 was established at >2000 mg/kg bw in male and female rats (Kaufmann, 1990).