Registration Dossier

In a guideline study, to GLP, rhodium (III) acetate “brown” (0.5 g) was applied to the shaved, 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 a primary irritation index of 0.3 (very slight but reversible erythema observed in two animals). No eschar formation, oedema, or systemic toxicity was apparent (Mayr, 1986c).
In a guideline study, to GLP, rhodium (III) acetate “brown” (0.1 g) produced a primary irritation index of 42 (out of 110) following instillation into the conjunctival sac of three rabbits and, therefore, was considered as moderately irritant in this test system (Mayr, 1986d).
No relevant respiratory tract irritation data were identified.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 March 1986 – 14 March 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD guideline No. 404 and to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Asta-Werke AG, D-4800 Bielefeld 14
- Age at study initiation: 4-6 months
- Weight at study initiation: 2.10-2.15 kg
- Housing: individually in ASTA Model stainless steel cages
- Diet (e.g. ad libitum): standard diet, ssniff K “special diet for rabbits” supplied by ssniff Spezialfutter GmbH D-4770 Soest, frequency of feeding not mentioned
- Water: ad libitum
- Acclimation period: 1 day before application of test material

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 6 am-6 pm fluorescent tube lighting, 6 pm-6 am “natural light-dark-rhythm”

Type of coverage:

occlusive

Preparation of test site:

shaved

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): 0.25 ml
- Purity: demineralised

Duration of treatment / exposure:

4 hrs

Observation period:

1, 24, 48 and 72 hrs after removal of the patch

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal skin area between shoulder and sacrum
- % coverage: not specified
- Type of wrap if used: The site of application was covered with approx. 6.25 cm2 of a linen cloth which adhered to a synthetic film glue. A bandage (Acrylastic, No. 2408, width 8 cm) was wrapped several times around the trunk to provide a complete occlusion.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Erythema (and eschar) formation and oedema formation were assessed qualitatively and quantitatively on the skin of 3 rabbits using the Draize method, 1, 24, 48 and 72 hrs after removal of the patch. The cutaneous irritation index at the four time points was determined separately for erythema (and eschar) formation and oedema formation, based on the arithmetical mean values of the individual grades. The irritation index was graded in a modified method according to Gilman et al:

Irritation index Evaluation
0.0-0.5 non-irritant
0.6-3.0 slightly irritant
3.1-5.0 moderately irritant
5.1-8.0 severely irritant

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 0.3

Max. score:

8

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 0.25

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

other: Very slight erythema (grade 1) was seen at 1 hour after removal of the patches in two of the rabbits and was still evident at 24 hours in one of these animals. Recovery was complete at 48 hrs.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 0

Max. score:

4

Irritant / corrosive response data:

Only very slight erythema (grade 1) was seen in two of the three rabbits and complete recovery occurred within 24 and 48 hrs after removal of the patches. There was no evidence of oedema.

Other effects:

There was no evidence of any systemic toxicity following dermal application.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, rhodium (III) acetate “brown” (0.5 g) was applied to the shaved, 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 a primary irritation index of 0.3 (very slight but reversible erythema observed in two animals). No eschar formation, oedema, or systemic toxicity was apparent.

Executive summary:

In an OECD Test Guideline 404 study, rhodium (III) acetate “brown” was investigated for irritant (and corrosive) effects following a 4-hr (occluded) application (0.5 g) to the shaved, intact skin of three female White Russian rabbits. The test sites were quantitatively and qualitatively assessed for erythema (and eschar) formation and oedema 1, 24, 48 and 72 hrs after removal of the patches.

The overall skin irritation score was 0.3. Very slight erythema (grade 1) was seen in two animals but the findings had completely disappeared 48 hr after removal of the patches. No eschar formation or oedema was seen in any animal and no systemic-toxic effects were apparent.

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

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 April 1986 – 22 April 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD guideline No. 405 and 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 (incl. QA statement)

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Asta-Werke AG, D-4800 Bielefeld 14
- Age at study initiation: 4-8 months
- Weight at study initiation: 2.0-2.3 kg
- Housing: individually
- Diet: ad libitum standard diet, ssniff K “special diet for rabbits” supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water: ad libitum
- Acclimation period: 1 day before application of test material

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 6 am-6 pm fluorescent tube lighting, 6 pm-6 am “natural light-dark-rhythm”

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Eye not rinsed, therefore 15 days

Observation period (in vivo):

1, 24, 48 and 72 hrs post application and thereafter once daily to day 15 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 an irritation index (see below):

Irritation index Evaluation
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, Hanover.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 42

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Hair loss around the eyes was still evident at 15 days post-application.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 27.5

Max. score:

80

Reversibility:

fully reversible within: 9 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 3.8

Max. score:

10

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hrs

Score:

ca. 10.5

Max. score:

20

Reversibility:

fully reversible within: 14 days

Other effects:

During the first week of observation there was discharge which moistened the lids and hairs just adjacent to the lids and considerable areas around the eyes. Also loss of hair around the eyes occurred. There were no systemic toxic effects and the general condition of the animals was unaffected after conjunctival instillation of the test material.

Table 1: Individual irritation scores for each timepoint.

Eye reaction	Time after exposure/hr	Draize score
		Animal 1	Animal 2	Animal 3
Corneal opacity	1	0	2	1
	24	1	2	1
	48	1	2	2
	72	1	2	2
Corneal area	1	0	3	4
	24	4	4	4
	48	4	4	4
	72	4	4	4
Iris	1	0	1	0
	24	1	1	1
	48	1	1	1
	72	0	1	1
Conjunctival redness	1	1	0	1
	24	2	2	3
	48	3	3	3
	72	3	3	3
Chemosis	1	0	2	1
	24	1	2	1
	48	1	2	2
	72	1	2	2
Discharge	1	0	1	1
	24	2	3	2
	48	1	2	2
	72	1	2	2

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, rhodium (III) acetate “brown” (0.1 g) produced a primary irritation index of 42 (out of 110) following instillation into the conjunctival sac of three rabbits and, therefore, was considered as moderately irritant in this test system.

Executive summary:

In an OECD Test Guideline 405 study, conducted according to GLP, rhodium (III) acetate “brown” (0.1 g) was instilled into the conjunctival sac of one 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 assessed, without rinsing, both quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale after 1, 24, 48 and 72 hr and once daily, thereafter, for up to 15 days post-application.

The sum of the scores at observation times 1, 24, 48 and 72 hrs was combined to give an irritation index of 42 (out of 110) and the test material was, therefore, considered as moderately irritant in this test system. All three animals displayed conjunctival redness scores (averaged over 24, 48 and 72-hr time points) of at least 2, while in two animals corneal opacity scores were above 1 and chemosis scores were at least 2. The observed irritation was fully reversible within the 15-day observation period. As well as the irritant effects, a discharge with moistening of the lids and hairs adjacent to the lids or considerable areas around the eye arose during the first week of observation, while beyond this time there was loss of hair around the eye. No corrosive effects or systemic toxicity were observed, and the general condition of the animals was unaffected by treatment.

Based on the results of this study, the test material would be classified as irritating to the eyes (Category 2) according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

No relevant irritation/corrosion human data were identified.

In an OECD Test Guideline 404 study, rhodium (III) acetate “brown” was investigated for irritant (and corrosive) effects following a 4-hr (occluded) application (0.5 g) to the shaved, intact skin of three female White Russian rabbits. The test sites were quantitatively and qualitatively assessed for erythema (and eschar) formation and oedema 1, 24, 48 and 72 hrs after removal of the patches. The overall skin irritation score was 0.3. Very slight erythema (grade 1) was seen in two animals but the findings had completely disappeared 48 hr after removal of the patches. No eschar formation or oedema was seen in any animal and no systemic-toxic effects were apparent (Mayr, 1986c).

In an OECD Test Guideline 405 study, conducted according to GLP, rhodium (III) acetate “brown” (0.1 g) was instilled into the conjunctival sac of one 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 assessed, without rinsing, both quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale after 1, 24, 48 and 72 hr and once daily, thereafter, for up to 15 days post-application. The sum of the scores at observation times 1, 24, 48 and 72 hrs was combined to give an irritation index of 42 (out of 110) and the test material was, therefore, considered as moderately irritant in this test system. All three animals displayed conjunctival redness scores (averaged over 24, 48 and 72-hr time points) of at least 2, while in two animals corneal opacity scores were above 1 and chemosis scores were at least 2. The observed irritation was fully reversible within the 15-day observation period. As well as the irritant effects, a discharge with moistening of the lids and hairs adjacent to the lids or considerable areas around the eye arose during the first week of observation, while beyond this time there was loss of hair around the eye. No corrosive effects or systemic toxicity were observed, and the general condition of the animals was unaffected by treatment (Mayr, 1986d).

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.

Effects on eye irritation: moderately irritating

Based on the results of the available reliable skin and eye irritation studies (in rabbits), rhodium acetate need not be classified for skin irritation, but should be classified as an eye irritant (category 2), according to EU CLP criteria (EC 1272/2008).