Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-04-28 to 1998-05-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD) and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(triphenylphosphine)rhodium (I) chloride
EC Number:
238-744-5
EC Name:
Tris(triphenylphosphine)rhodium (I) chloride
Cas Number:
14694-95-2
Molecular formula:
C54H45ClP3Rh
IUPAC Name:
rhodium;triphenylphosphane;chloride
Details on test material:
- Name of test material (as cited in study report): Chlorotris-(triphenylphosphine)-rhodium(I)
- Physical state: red, crystalline solid
- Analytical purity: Not indicated by sponsor
- Isomers composition: no data
- Lot/batch No.: Not indicated by sponsor
- Stability under test conditions: “the test substance was stable throughout the experimental period”
- Storage condition of test material: no data

Test animals

Species:
rabbit
Strain:
other: White Russian (albino)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG, D-4800, Bielefeld 14
- Age at study initiation: 4-6 months
- Weight at study initiation: 2.0-2.7 kg
- Housing: ASTA Model stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-22.5
- Humidity (%): 40-65
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
other: intact
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.3 ml
Duration of treatment / exposure:
Single 4 hour exposure
Observation period:
6 days
Number of animals:
3 (2 males and 1 female)
Details on study design:
TEST SITE
- Type of wrap if used: The site of application was covered with a linen cloth (about 6.25 cm2) which adhered to a synthetic film glue. The opposite area of the dorsal skin was treated in the same way but without administration of the test material (control site). A bandage wrapped several times around the trunk provided complete occlusion.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: Patches removed after 4 hours.

SCORING SYSTEM: The treated skin area was qualitatively and quantitatively scored using the Draize method at 1, 24, 48, and 72 hrs, and thereafter daily, following removal of the patches (see OECD guidelines for grading of skin reactions). The individual values for erythema/eschar formation and oedema at the 1, 24, 48, and 72-hr readings were added separately and divided by 12. The primary irritation index is given by the sum of these two mean values.

The following gradation was allocated to this index by a modified method from Gilman et al. (1983):
Primary irritation index Gradation
0.0-0.5 non-irritant
0.6-3.0 slight irritant
3.1-5.0 moderate irritant
5.1-8.0 severe irritant

In addition, attention was paid to the occurrence of other skin reactions and irreversible alteration of the dermal tissue (which would lead to a classification of corrosive effects) and systemic toxic effects.

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 0.9
Max. score:
8
Reversibility:
fully reversible within: 6 days for erythema
Remarks on result:
other: Very slight erythema seen in all animals. No eschar formation or oedema seen.
Irritant / corrosive response data:
Very slight erythema (barely perceptible) (a score of 1) was noted in all three rabbits assessed at 24, 48 and 72 hr after patch removal, in two rabbits assed after 1 hr, and in two rabbits assessed 4 days after patch removal.
Other effects:
One animal reacted with skin scales, which immediately peeled off. After removal of the patch, brownish colouration of the application site was noted in one animal. No systemic-toxic effects were seen and the general condition of the test animals was not affected.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline study, to GLP, chlorotris-(triphenylphosphine)-rhodium(I) was applied to the intact skin of three rabbits (4-hr occluded) and irritant reactions were assessed 1, 24, 48, and 72-hr after patch removal. The test item produced an overall primary irritation index of 0.9 (very slight but reversible erythema observed in all animals). No eschar formation, oedema, or systemic toxicity was apparent.
Executive summary:

In an OECD Test Guideline 404 study, conducted according to GLP, chlorotris-(triphenylphosphine)-rhodium(I) was investigated for irritant (and corrosive) effects following its 4-hr (occluded) application (0.5 g) to the intact dorsal skin of three White Russian rabbits (two males and one female). The test sites were observed for signs of erythema/eschar formation and oedema using the Draize grading scores, at 1 hr, and then daily for up to six days, after patch removal. The opposite area of the dorsal skin was treated in the same way, but without application of the test substance (control site).

 

Very slight erythema (a score of 1) was noted in all animals assessed at 24, 48 and 72-hrs after patch removal, in two rabbits assed after 1 hr, and in two rabbits assessed 4-days after patch removal. No such findings were seen from day 6 of observation. No eschar formation or oedema was seen in any animal. One rabbit reacted with skin scales, which immediately peeled off. Brownish colouration of the application site was noted in one animal. No systemic-toxic effects were seen and the general condition of the test animals was not affected.

 

Based on the results of this study, no classification for skin irritation is required according to EU CLP criteria (EC 1272/2008).