Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
points 8.1 and 8.2 of Annex VIII of REACH have been amended. Nevertheless, adequate information from existing in vivo skin irritation or eye irritation studies can still be used to fulfil the information requirement at any tonnage level.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From the 13th to the 20th of April, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted according to internationally accepted guideline

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 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Environmental fate/Ecotoxicological/Toxicological studies:
Storage: Room temperature, 20-24 °C, in the dark
Stability: pure, for 5 years; in solvent > 24 hours in water, DMSO, DMF, stable for at least 2 hours in aqueous medium.
Evidence of chemical instability at pH 6: none
Safety precaution: routine hygienic procedures were sufficient to assure personnel health and safety.
Toxicological studies:
Preparation: On the day of the experiment, the test article was suspended in Carboxymethylcellulose (1 %).
The vehicle was chosen to its nontoxicity for the animals. All animals received a single standard dose volume of 10 mL/kg body weight orally.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf
Number of animals: 1 male, 2 females
Age at start of treatment: male, 15 weeks, females 16 weeks
Body weight at start of or treatment: male, 3.0 kg, females: 3.2 kg
Identification: by unique cage number and corresponding ear tags.
Acclimatization: four days under test conditions after veterinary examination.
Allocation: Animal Numbers, Male no, 1 Female nos. 2, 3

HUSBANDRY
Room No,: 138
Standard Laboratory Conditions.
Air-onditioned with 10-15 air changes per hour and hourly monitored environment with temperature 20±3 °C, relative humidity 40-70%, 12 hours
artificial fluorescent light/12 hours dark, music/light period.
Accommodation: individually in stainless steel cages equipped with an automatic cleaning and drinking system.
Diet: pelleted standard Kliba 341, Batch 52/90 rabbit maintenance diet (“Kliba”, Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum,
Analysis for contaminants performed.
Water: community tap water from Itingen, ad libitum
Analysis for contaminants performed.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Controls:
no
Amount / concentration applied:
0.5 g of the test article
Duration of treatment / exposure:
4 hours
Observation period:
Viability, mortality: daily
Body weight: Start of acclimatization, day 1 of test (application day) and at termination of observation.
The skin reaction was assessed at 1, 24, 48 and 72 hours intervals after the removal of the dressing, gauze patch and test article.
Number of animals:
1 male
2 females
Details on study design:
Approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). The skin of the animals was observed 1 day prior to test article administration.
On test day 1, 0.5 g of the test article was applied to approx. 6 cm^2 of the intact skin of the shaved area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi—occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage.
Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed according to the following numerical scoring system.
The observation was terminated 72 hours after application of the test article.
All rabbits were killed by an intravenous injection of T61 (Hoechst AG) into the ear vein and discarded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The substance showed a primary irritation score of 0.00 when applied to intact rabbit skin. Local signs (mean 1 hour to 72 hours/day) consisted or grade 0.00 erythema and grade 0.00 edema.
No destructions or irreversible alterations or the treated skin were observed. No corrosive effect was evident on the skin.
In the area of application yellowish staining of the treated skin by pigment or coloring of the test article was observed in all animals between 1 to 72 hours
(termination or the study).
Other effects:
The body weight gain of all rabbits was similar.
No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.
No necropsy was performed. All animals were killed and discarded.

Any other information on results incl. tables

Data are summarized in tabular form, showing for each individual animal the irritation scores for erythema and edema at 60 minutes, 24, 48 and 72 hours after patch removal, any lesions, a description or the degree and nature of irritation, corrosion or reversibility, and any other toxic effects observed. The dermal irritation scores were evaluated in conjunction with the nature and reversibility or otherwise of the responses observed. The individual scores do not represent an absolute standard for the irritant properties of a material, and they are viewed as reference values. The use of a semi-occlusive dressing is a severe test and the results are not directly comparable to human exposure conditions.

Mean values and standard deviations were calculated whenever possible.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Classification criteria according to the CLP Regulation 1272/2008 and its amendments
Conclusions:
Non irritant/corrosive for the skin
Executive summary:

Materials and methods

The irritation/corrosion property was tested on the substance according to the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and the EU Method B.4 (Acute Toxicity: Dermal Irritation/Corrosion), in GLP.

Under the conditions of the experiment, the tested substance was found to cause a primary irritation score of 0.00 when applied to intact rabbit skin. No corrosive effect had occurred on the skin at any measuring interval.

Local signs (mean 1 hour to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.

In the area of application, yellowish staining of the treated skin by pigment or coloring of the test article was observed in all animals until termination.

Observations

According to EEC Council Directive, 83/467/EEC, the mean value of the scores for each type of lesion, calculated for each animal separately, is the following:

Mean 24-72 hours 0.00 (Erythema, Edema), all the animals (1 male, 2 females).

Conclusions

Due to the results described above, the substance is considered non irritant to the skin of rabbits.