Dicarbonyl(pentane-2,4-dionato-O,O')rhodium

Endpoint summary

Description of key information

In an in vivo skin irritation study, rhodium dicarbonyl acetylacetonate (0.5 mL) produced a primary irritation index of 0.7 following 24-hr occlusive application to the shaved abraded and intact skin of six rabbits. This study was not performed to current OECD guidelines (Middleton & Haynes, 1977).

In an in vivo eye irritation study, undiluted rhodium dicarbonyl acetylacetonate (0.1 g) produced eye irritation in all six treated albino rabbits, following a 72-hr observation period. The reversibility of the lesions (after 21 days) was not investigated (Middleton, 1978).

No relevant respiratory tract 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study apparently performed according to the method described in Federal Register 1973, Vol. 38, No. 187, Section 1500:41, which has some significant deviations from current OECD guidelines. Limited reporting, notably of test material (e.g. purity).

Qualifier:

according to guideline

Guideline:

other: Skin irritation patch test, as described in Federal Register 1973, Vol. 38, No. 187, Section 1500:41.

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: “recognised breeders”
- Age at study initiation: 16-18 weeks
- Weight at study initiation: 2.2-2.4 kg
- Housing: unspecified numbers per cage
- Diet: ad libitum commercial rabbit diet supplied by Rank Hovis MacDougal
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): “natural lighting conditions”

Type of coverage:

occlusive

Preparation of test site:

other: Backs of the rabbits were shaved (not “closely clipped” as recommended by the OECD guidelines). One site of each rabbit was abraded immediately before application of the test material, the other site remained intact.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hrs

Observation period:

48 hrs after removal of the patch

Number of animals:

six

Details on study design:

TEST SITE
- Area of exposure: Each site 2.5 cm2 (one intact, one abraded)
- % coverage: at least 10%
- Type of wrap if used: Gauze pad was secured by “Sleek” adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: Erythema (and eschar) formation and oedema formation were assessed on the intact and abraded skin of six rabbits at 24 and 72 hr after initial application of the test compound (i.e. as soon as the dressing was removed and again 48 hrs later). The primary irritation index was calculated by adding the four values for erythema (and eschar) formation to the four for oedema formation, and dividing the total by four. According to the study report, Draize (1959) considers that “compounds producing combined averages (primary irritation indices) of 2 or less are only mildly irritating; whereas those with indices of 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants”.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs after initial application

Score:

0.7

Max. score:

8

Reversibility:

other: Reversibility not assessed, as observation period only 48 hrs (not up to 14 days as recommended in the OECD guidelines). However, on the majority of occasions where irritation (score of 1 or 2) was noted after dressing removal, the severity of the irritat

Remarks on result:

other: Average score for abraded and intact skin

Irritant / corrosive response data:

On the intact skin, slight erythema was seen in two (out of 6) rabbits assessed after dressing removal, which was still observed on one of these animals assessed 48 hours later. No oedema was reported on the intact skin of any treated animals assessed at either time point (0 or 48 hours after dressing removal).

Other effects:

No further effects were reported.

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo skin irritation study, rhodium dicarbonyl acetylacetonate (0.5 mL) produced a primary irritation index of 0.7 following 24-hr occlusive application to the shaved abraded and intact skin of six rabbits. This study was not performed to current OECD guidelines.

Executive summary:

Rhodium dicarbonyl acetylacetonate (0.5 ml) was applied (occluded) to the shaved abraded and intact skin of six albino rabbits. After 24 hrs, the dressings were removed and the sites were quantitatively assessed for erythema (and eschar) formation and oedema formation. Similar assessments were made 48 hrs later. The sum of these values was combined and divided by four to give a primary irritation score of 0.7 (out of a possible 8).On the intact skin, slight erythema (but no oedema) was seen in two rabbits assessed after dressing removal, which was still observed on one of these animals assessed 48 hours later. Overall, rhodium dicarbonyl acetylacetonate was mildly irritating in this test system as there was a tendency for reversibility of effects over time.

 

This study suffered from a number of significant deviations from the recommendations given in the current OECD guidelines. These included use of abraded skin, a longer exposure period, failure to wash off any residual test material after removal of the dressing, an insufficient observation period to assess reversibility of effects, and the skin was only examined on two occasions (at 0 and 48 hrs), rather than at 1, 24, 48 and 72 hrs after patch removal. However, certain of these deviations would have likely increased the possibility of an irritant reaction .

 

Mean erythema and oedema scores were below 2.3 for all six animals. Accordingly, rhodium dicarbonyl acetylacetonate does not require classification for skin irritation 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Eye test carried out to guideline (US). Limited reporting, notably of test material (e.g. purity).

Qualifier:

according to guideline

Guideline:

other: As described in US Federal Register 1973 Eye test.

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Affected animals terminated after 3 days - lesion progression/reversibility not assessed

GLP compliance:

no

Remarks:

Predates GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: "Recognised breeders"
- Age at study initiation: 14-16 weeks
- Weight at study initiation: 2.2 kg
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

other: right eye treated; left eye untreated - control

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

up to 72 hours

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize method - corneal opacity, iris inflammation, conjunctival irritation

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

corrected cumulative score

Time point:

other: 24, 48, 72 hours

Score:

6.4

Max. score:

80

Reversibility:

not specified

Remarks on result:

other: See Tables 1 and 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

corrected cumulative score

Time point:

other: 24, 48, 72 hours

Score:

2.5

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: See Tables 1 and 2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

corrected cumulative score

Time point:

other: 24, 48, 72 hours

Score:

7.5

Max. score:

20

Reversibility:

not specified

Remarks on result:

other: See Tables 1 and 2

Irritant / corrosive response data:

Corneal damage was seen in two of the treated animals at all time points, and in an additional animal at 72 hours. Effects on the iris of four animals was seen at 24 hours but in only two animals at 72 hours. All 6 animals showed redness to the conjunctivae after 24 and 48 hours, the effect also being seen in 5/6 animals at 72 hours. Chemosis and conjunctival discharge was seen in three animals at all time points examined and in one (chemosis) and two (discharge) at 24 hours only. See Table 1 for total and average scores.

Other effects:

No data

Table 1. Individual scores for the group of 6 rabbits

No.	Time/hr	Cornea		Iris	Conjunctivae			Corrected score			Total
		O	A		R	Ch.	Dis.	Cr.	Ir.	Cj.
1	24	1	4	1	1	2	3	20	5	12	37
	48	2	2	1	2	1	1	20	5	8	33
	72	1	4	0	1	2	2	20	0	10	30
2	24	0	0	0	2	1	2	0	0	10	10
	48	Dull	Dull	0	2	0	0	0	0	4	4
	72	0	0	0	1	0	0	0	0	2	2
3	24	0	0	1	2	0	1	0	5	6	11
	48	0	0	0	1	0	0	0	0	2	2
	72	0	0	0	1	0	0	0	0	2	2
4	24	0	0	0	2	0	0	0	0	4	4
	48	0	0	0	1	0	0	0	0	2	2
	72	0	0	0	0	0	0	0	0	0	0
5	24	0	0	1	2	2	2	0	5	12	17
	48	Dull	Dull	1	3	2	1	0	5	12	17
	72	1	2	1	2	2	2	0	5	12	17
6	24	1	3	1	2	3	2	15	5	14	34
	48	1	3	1	3	2	1	15	5	12	32
	72	1	3	1	1	2	2	15	5	10	30

O: Opacity; A: Area; R: Redness; Ch.: Chemosis; Dis.: Discharge; Cr.: Cornea; Ir.: Iris; Cj.: Conjunctivae

Table 2. Total and average score for the group of 6 rabbits

Time	Cornea	Iris	Conjunctivae	Total
24 hours	35	20	59	114
48 hours	35	15	40	90
72 hours	45	10	36	91
Total	115	45	135	295
Average	19.2	7.5	22.5	49.2

All 6 rabbits showed a positive response

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In an in vivo eye irritation study, undiluted rhodium dicarbonyl acetylacetonate (0.1 g) produced eye irritation in all six treated albino rabbits, following a 72-hr observation period. The reversibility of the lesions (after 21 days) was not investigated, though the general trend in the irritation scores suggests classification as an eye irritant (category 2) is appropriate.

Executive summary:

In a US guideline in vivo eye irritation study, undiluted rhodium dicarbonyl acetylacetonate (0.1 g) was instilled into the right eye of 6 female New Zealand white rabbits. The animals were assessed for signs of irritation after 24, 48 and 72 hr and the data scored according to the Draize method. The eyes of the treated animals were not rinsed at any time and no observations beyond 72 hours were made.

 

Corneal damage was seen in two of the treated animals at all observation points, and in an additional animal at 72 hr. Effects on the iris of four animals was seen at 24 hours but in only two animals at 72 hours. All 6 animals showed redness to the conjunctivae after 24 and 48 hours, the effect also being seen in 5/6 animals at 72 hours. Chemosis and conjunctival discharge was seen in three animals at all time points examined and in one (chemosis) and two (discharge) at 24 hours only.

 

The reversibility of the lesions (after 21 days) was not investigated. However, the iris and conjunctivae scores showed a general decrease over the three time periods. While the corneal scores were slightly increased at 72 hr due to reactions in a single animal, effects were consistent across the time points in two animals and no corneal effects were observed in the remaining three animals at any time point.

 

The investigators concluded that as all 6 treated animals showed a positive response to the test material it would be classified as an eye irritant according to the US Federal register 1973 Eye Test.

 

All six rabbits showed respective scores for iritis and corneal opacity of less than 1.5 and 3. While the observation period was limited to 3 days (OECD guideline recommends 21 days), there is sufficient evidence to indicate a general reversibility in the observed effects. As such, classification of rhodium dicarbonyl acetylacetonate as an eye irritant (category 2), is appropriate on the basis of the findings of this study and according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant irritation/corrosion human data were identified.

 

Rhodium dicarbonyl acetylacetonate (0.5 ml) was applied (occluded) to the shaved abraded and intact skin of six albino rabbits. After 24 hrs, the dressings were removed and the sites were quantitatively assessed for erythema (and eschar) formation and oedema formation. Similar assessments were made 48 hrs later. The sum of these values was combined and divided by four to give a primary irritation score of 0.7 (out of a possible 8).On the intact skin, slight erythema (but no oedema) was seen in two rabbits assessed after dressing removal, which was still observed on one of these animals assessed 48 hours later. Overall, rhodium dicarbonyl acetylacetonate was mildly irritating in this test system as there was a tendency for reversibility of effects over time. This study suffered from a number of significant deviations from the recommendations given in the current OECD guidelines. These included use of abraded skin, a longer exposure period, failure to wash off any residual test material after removal of the dressing, an insufficient observation period to assess reversibility of effects, and the skin was only examined on two occasions (at 0 and 48 hrs), rather than at 1, 24, 48 and 72 hrs after patch removal. However, certain of these deviations would have likely increased the possibility of an irritant reaction (Middleton & Haynes, 1977).

 

In a US guideline in vivo eye irritation study, undiluted rhodium dicarbonyl acetylacetonate (0.1 g) was instilled into the right eye of 6 female New Zealand white rabbits. The animals were assessed for signs of irritation after 24, 48 and 72 hr and the data scored according to the Draize method. The eyes of the treated animals were not rinsed at any time and no observations beyond 72 hours were made. Corneal damage was seen in two of the treated animals at all observation points, and in an additional animal at 72 hr. Effects on the iris of four animals was seen at 24 hours but in only two animals at 72 hours. All 6 animals showed redness to the conjunctivae after 24 and 48 hours, the effect also being seen in 5/6 animals at 72 hours. Chemosis and conjunctival discharge was seen in three animals at all time points examined and in one (chemosis) and two (discharge) at 24 hours only. The reversibility of the lesions (after 21 days) was not investigated. However, the iris and conjunctivae scores showed a general decrease over the three time periods. While the corneal scores were slightly increased at 72 hr due to reactions in a single animal, effects were consistent across the time points in two animals and no corneal effects were observed in the remaining three animals at any time point (Middleton, 1978).

 

No respiratory tract data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement.

Justification for classification or non-classification

Mean erythema and oedema scores were below 2.3 for all six animals. Accordingly, dicarbonyl(pentane-2,4-dionato-O,O')rhodium does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

 

All six rabbits showed scores for corneal opacity and iritis of less than three and 1.5 respectively. While the observation period was limited to 3 days (guideline recommends 21 days), there is sufficient evidence to indicate a general reversibility in the observed effects. As such, classification of dicarbonyl(pentane-2,4-dionato-O,O')rhodium as an eye irritant (category 2), is appropriate on the basis of the findings of this study and according to EU CLP criteria (EC 1272/2008).