Carbonylhydrotris(triphenylphosphine)rhodium

Endpoint summary

Description of key information

In a guideline study, to GLP, carbonylhydridotris(triphenylphosphane)-rhodium(I) was not irritating to the skin of rabbits following a 4-hr occlusive application (Zechel, 1990).
In a guideline study, to GLP, carbonylhydridotris(triphenylphosphane)-rhodium(I) was not irritating to rabbit eyes following instillation of 0.038 or 0.032 g (volume 0.1 mL) of the test material to the conjunctival sac of 3 animals (Berthold, 1991b).
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:

Not stated

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 404)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The humidity went down to 30% “for a short period; this deviation was without any influence on the results of the study”. Also, the patch was occluded, rather than semi-occluded.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

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

- Age at study initiation: 7-12 months

- Weight at study initiation: 2.59-2.77 kg

- Housing: Stainless steel cages with grating floor, size 48.5 cm(l) x 40 cm (b) x 36.5 cm (h); 1/cage

- Diet (e.g. ad libitum): Standard diet, Ssniff K, special diet for rabbits; ~120 g/day per animal

- Water (e.g. ad libitum): municipal drinking water, automatic drinking water system with drinking nipples; ad libitum

- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22.5

- Humidity (%): 30-70

- Air changes (per hr): not stated

- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: not stated

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: control area on opposite flank of each treated animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

- Concentration (if solution): not applicable, moistened

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable, enough to moisten test material

- Concentration (if solution): not applicable, moistened

- Lot/batch no. (if required): not applicable

- Purity: demineralised water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after patch removal (all 3 animals), then daily to day 6 (1 animal)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: ~6.25 cm2

- % coverage: not stated

- Type of wrap if used: site of application covered with linen cloth which adhered to a synthetic film glue; bandage wrapped several times around the trunk providing complete occlusion

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, at end of exposure period

- Time after start of exposure: 4 hours

SCORING SYSTEM: Qualitative and quantitative assessment using Draize method - erythema/eschar and oedema, both scored on a scale of 0-4; also occurrence of further reactions of the skin (e.g. corrosive effects) and clinical signs (indicating systemic toxicity)

Irritation index calculated from sum of mean values of individual scores at the 4 observation times for erythema/eschar and for oedema; graded using modification of the method of Gilman et al., 1983

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: All time points: 1, 24, 48 and 72 hours, 4 and 6 days

Score:

ca. 0

Max. score:

8

Irritant / corrosive response data:

Erythema/eschar: 0 at all time points in all animals
Oedema: 0 at all time points in all animals.
Corrosion: no effects noted
Corresponding control patch on opposite flank of each animal: no reactions

Other effects:

No systemic effects observed.

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, to GLP, carbonylhydridotris(triphenylphosphane)-rhodium(I) was not irritating to the skin of rabbits following a 4-hr occlusive application.

Executive summary:

The skin irritation potential of carbonylhydridotris(triphenylphosphane)-rhodium(I) was evaluated in White Russian rabbits in a study conducted according to OECD Test Guideline 404 and to GLP.

 

The test material (0.5 g, moistened with water) was applied to the shaved dorsal skin of 3 animals, covered for 4 hours (occluded) and washed off. Skin reactions were evaluated 1, 24, 48 and 72 hours after patch removal and, in 1 animal, at 4 and 6 days. No erythema/eschar or oedema was observed at any time point in any animal. No corrosive effects or systemic toxicity was noted. Carbonylhydridotris(triphenylphosphane)-rhodium(I) produced a primary dermal irritation index of 0 and was not irritating to the skin of rabbits under the conditions of the test.

 

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:

Not stated but QA inspections on 07-Jan-1991 and 15-Jan-1991 during the experimental phase

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

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

Species:

rabbit

Strain:

other: White Russian (Albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG

- Age at study initiation: male 8 months, females 8 and 10 months

- Weight at study initiation: male 2.74 kg, females 2.90 and 3.17 kg

- Housing: stainless steel cages with grating floor, type ASTA, 48.5 cm (l) x 40 cm (b) x 36.5 cm (h); 1/cage

- Diet (e.g. ad libitum): ~120 g/animal per day; standard diet, Ssniff K, special diet for rabbits

- Water (e.g. ad libitum): municipal water supply, using an automatic drinking water system with drinking nipples, ad libitum

- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23

- Humidity (%): 40-55

- Air changes (per hr): not stated

- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Not stated but QA inspections on 07-Jan-1991 and 15-Jan-1991 during the experimental phase

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of each animal was not treated and acted as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.038 or 0.032 g (approximate volume 0.1 ml)
- Concentration (if solution): not applicable

VEHICLE: none

Duration of treatment / exposure:

Treated eyes not rinsed but physiological processes would be expected to result in the removal of the test substance

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done
- Time after start of exposure: not applicable

SCORING SYSTEM: Observations made at 1, 24, 48 and 72 after application of test material; signs of irritation assessed qualitatively and quantitatively using Draize scale - cornea (opacity 0-4, area involved 1-4), iris (0-2) and conjunctiva (redness 0-3, chemosis 0-4, discharge 0-3); irritation index calculated as the sum of these scores (0-110); graded according to Gilman et al., 1983

TOOL USED TO ASSESS SCORE: Cliptrix pencil light

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

80

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

10

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

2.3

Max. score:

20

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Overall irritation index: 2;
Cornea - opacity and area involved: 0 for all 3 animals at all 4 time points;
Iris: 0 for all 3 animals at all 4 time points;
Conjunctiva - redness - 1, 24, 48 and 72 hours: 1, 2, 1 and 0 (#1), 1, 1, 0, 0 (#2), 0, 1, 1 0 (#3);
Conjunctiva - chemosis: 0 for all 3 animals at all 4 time points;
Conjunctiva - discharge: 2 for all 3 animals at 1 hour, 0 for all 3 animals at all other time points;
No effects in untreated eye of each animal

Other effects:

No systemic toxicity; no effect on general condition of animals

Table 1: Individual irritation scores

Ocular lesions	Time after exposure/hr	Draize grade
		Animal 1	Animal 2	Animal 3
Corneal opacity	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
Corneal area	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
Iris	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
Conjunctival redness	1	1	1	0
	24	2	1	1
	48	1	0	1
	72	0	0	0
Conjunctival chemosis	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
Conjunctival discharge	1	2	2	2
	24	0	0	0
	48	0	0	0
	72	0	0	0

EU criteria: classification in category 2 applies when a positive response is seen in >=2/3 treated animals at >=1 for cornea and/or >=1 for iris and/or >=2 conjunctival redness and/or >=1 for conjunctival oedema, calculated as a mean score at 24, 48 and 72 hours

 

This calculation produces mean values of 0 for cornea for all 3 animals, 0 for iris for all 3 animals, 1, 0.3 and 0.7 for conjunctival redness for the 3 animals respectively, 0 for conjunctival discharge; therefore category 2 does not apply and the test material is classified as non-irritant by EU criteria

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, to GLP, carbonylhydridotris(triphenylphosphane)-rhodium(I) was not irritating to rabbit eyes following instillation of 0.038 or 0.032 g (volume 0.1 mL) of the test material to the conjunctival sac of 3 animals.

Executive summary:

The eye irritation potential ofcarbonylhydridotris(triphenylphosphane)-rhodium(I) was evaluated in White Russian rabbits in a study conducted in accordance with OECD Test Guideline 405 and to GLP. A quantity of 0.038 or 0.032 g (volume 0.1 mL) of the test material was placed in the conjunctival sac of 3 animals. The other eye of each animal was not treated and acted as a control. The treated eyes were evaluated at 1, 24, 48 and 72 hr after application and scored for irritation of the cornea, iris and conjunctiva according to the Draize system.

 

No effects were seen on the cornea or iris of any animal at any time point. Slight or moderate redness was seen in the conjunctivae of all animals, but this had reversed after 72 hr. Moderate conjunctival discharge was seen in all animals at 1 hr, but this had reversed after 24 hr. No corrosive or systemic effects were noted.

 

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.

 

The skin irritation potential of carbonylhydridotris(triphenylphosphane)-rhodium(I) was evaluated in White Russian rabbits in a study conducted according to OECD Test Guideline 404 and to GLP. The test material (0.5 g, moistened with water) was applied to the shaved dorsal skin of 3 animals, covered for 4 hours (occluded) and washed off. Skin reactions were evaluated 1, 24, 48 and 72 hours after patch removal and, in 1 animal, at 4 and 6 days. No erythema/eschar or oedema was observed at any time point in any animal. No corrosive effects or systemic toxicity was noted. Carbonylhydridotris(triphenylphosphane)-rhodium(I) produced a primary dermal irritation index of 0 and was not irritating to the skin of rabbits under the conditions of the test (Zechel, 1990).

 

The eye irritation potential ofcarbonylhydridotris(triphenylphosphane)-rhodium(I) was evaluated in White Russian rabbits in a study conducted in accordance with OECD Test Guideline 405 and to GLP. A quantity of 0.038 or 0.032 g (volume 0.1 mL) of the test material was placed in the conjunctival sac of 3 animals. The other eye of each animal was not treated and acted as a control. The treated eyes were evaluated at 1, 24, 48 and 72 hr after application and scored for irritation of the cornea, iris and conjunctiva according to the Draize system. No effects were seen on the cornea or iris of any animal at any time point. Slight or moderate redness was seen in the conjunctivae of all animals, but this had reversed after 72 hr. Moderate conjunctival discharge was seen in all animals at 1 hr, but this had reversed after 24 hr. No corrosive or systemic effects were noted. Carbonylhydridotris(triphenylphosphane)-rhodium(I) was not irritating to the eyes of rabbits under the conditions of the test (Berthold, 1991b).

 

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 carbonylhydrotris(triphenylphosphine)rhodium for skin or eye irritation according to EU CLP criteria (EC 1272/2008).