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Description of key information

In a guideline study, to GLP, chlorotris-(triphenylphosphine)-rhodium(I), applied to the intact skin of three rabbits (4-hr occluded), 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 (Mayr, 1988b).
In a guideline eye irritation study, conducted to GLP, chlorotris-(triphenylphosphine)-rhodium(I) (0.07 g) produced a primary irritation index of 3 (out of 110) following application into the conjunctival sac of the right eye of three rabbits (Mayr, 1988c).
No relevant respiratory tract irritation data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
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
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

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.

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.
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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 May 1988 – 5 May 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guideline No. 405 and EEC guideline 84/449/EEC
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
other: White Russian (albino)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 4-5 months
- Weight at study initiation: 2.14-2.42 kg
- Housing: 1 animal/cage in stainless steel cages with grating floor
- Diet: ad libitum standard diet, ssniff K “special diet for rabbits” supplied by ssniff Spezialfutter GmbH, D-4770 Soest.
- Water: ad libitum
- Acclimation period: Animals kept 1 day under the test conditions before application of the test material.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-22.5
- Humidity (%): 40-55
- Photoperiod (hrs dark / hrs light): 6 am-6 pm artificial lighting, 6 pm-6 am “natural light-dark-rhythm”
Vehicle:
unchanged (no vehicle)
Controls:
other: No, although left eye of each animal remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.07 g
Duration of treatment / exposure:
Single instillation. Eye not rinsed, therefore possibly for 3 days
Observation period (in vivo):
1, 24, 48 and 72 hrs post application
Number of animals or in vitro replicates:
1 male and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: Signs of irritation on the cornea, iris and conjunctiva were assessed quantitatively and qualitatively using the Draize scale and the mean values of the individual grades at examination times 1, 24, 48 and 72 hrs expressed by a corresponding score. The irritation index is the sum of these scores. A corresponding graduation was allocated to this index using a modified method according to Gilman et al. (1983).

Index Ranges Gradation
0 – 10 non-irritant
11 – 25 slightly irritant
26 – 56 moderately irritant
57-110 severely irritant

TOOL USED TO ASSESS SCORE: Cliptrix pencil light (No. 645) supplied by Varta, D-3000 Hanover.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs
Score:
3
Max. score:
110
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
10
Reversibility:
other: Not applicable
Remarks on result:
other: No effects were reported on the iris.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
80
Reversibility:
other: Not applicable
Remarks on result:
other: No effects were reported on the cornea.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs
Score:
3
Max. score:
20
Reversibility:
fully reversible within: 48 hrs
Irritant / corrosive response data:
Examination of the conjunctiva revealed hyperemia (grade 1) or diffuse crimson redness (grade 2) during the first day of observation in all 3 animals. One animal also had slight swelling (grade 1). The findings were completely reversible and had disappeared 48 hrs after application. There was no evidence of any irritant effects on the cornea nor iris, nor any effects in the untreated eye.
Other effects:
During the first day of observation, discharge with moistening of lids and hairs or considerable areas around the eye was recorded. There were no systemic toxic effects and the general condition of the animals was undisturbed.
Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline eye irritation study, conducted to GLP, chlorotris-(triphenylphosphine)-rhodium(I) (0.07 g) produced a primary irritation index of 3 (out of 110) following application into the conjunctival sac of the right eye of three rabbits.
Executive summary:

In an OECD Test Guideline 405 study, conducted to GLP, chlorotris-(triphenylphosphine)-rhodium(I) (0.07 g) was instilled into the conjunctival sac of the right eye of one male and 2 female White Russian rabbits and both lids were briefly closed by gentle finger pressure. The other eye remained untreated and acted as the control. The treated eye was then assessed, quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale 1, 24, 48 and 72 hrs post application.

 

The sum of the scores at observation times 1, 24, 48 and 72 hrs was combined to give an irritation index of 3 (out of a possible 110). Slight signs of irritation in the conjunctivae (including hyperaemia, diffuse crimson redness and swelling) seen during the first day of observation, were fully reversible within 48 hours. No effects were seen in the iris or cornea. Chlorotris-(triphenylphosphine)-rhodium(I) was, therefore, classified as non-irritant in this test system. No corrosive effects or systemic toxicity were observed.

 

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No relevant irritation/corrosion human data were identified.

 

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 (Mayr, 1988b).

 

In an OECD Test Guideline 405 study, conducted to GLP, chlorotris-(triphenylphosphine)-rhodium(I) (0.07 g) was instilled into the conjunctival sac of the right eye of one male and 2 female White Russian rabbits and both lids were briefly closed by gentle finger pressure. The other eye remained untreated and acted as the control. The treated eye was then assessed, quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale 1, 24, 48 and 72 hrs post application. The sum of the scores at observation times 1, 24, 48 and 72 hrs was combined to give an irritation index of 3 (out of a possible 110). Slight signs of irritation in the conjunctivae (including hyperaemia, diffuse crimson redness and swelling) seen during the first day of observation, were fully reversible within 48 hours. No effects were seen in the iris or cornea. Chlorotris-(triphenylphosphine)-rhodium(I) was, therefore, classified as non-irritant in this test system. No corrosive effects or systemic toxicity were observed (Mayr, 1988c).

 

No relevant respiratory tract irritation data were identified.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, and the only skin irritation study available.

Justification for selection of eye irritation endpoint:
OECD guideline study, and the only eye irritation study available.

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies in rabbits, there is no requirement to classify tris(triphenylphosphine) rhodium(I) chloride for skin or eye irritation according to EU CLP criteria (EC 1272/2008).