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

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Limited reporting, notably of test material (e.g. purity). Also, due to the method of test sample preparation, there is some doubt as to the identity of what was actually tested. No (sub)classification possible.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study conducted in 1978

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

238-947-9

EC Name:

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

Cas Number:

14874-82-9

Molecular formula:

C7H7O4Rh

IUPAC Name:

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

Details on test material:

- Name of test material (as cited in study report): rhodium dicarbonyl acetylacetonate ("Sample CB23")
- Substance type: dark coloured metallic powder
- Physical state: solid

The test material (CB23 - rhodium dicarbonyl acetylacetonate) was prepared as a saturated solution in water obtained by heating at 50 deg C for 24 hours, then cooling to ambient temperature. See also under Overall remarks.

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Porcellus Animal Breeding Ltd, Heathfield, Sussex
- Weight at study initiation: 300-350 g
- Housing: caged, numbers not specified
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 ± 1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): “controlled lighting conditions”

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Saturated solution used for the intradermal injection induction procedure, 50% dilution in petrolatum used for the topical induction procedure, 5% dilution in petrolatum used for the 1st challenge dose and 1% dilution in petrolatum used for the 2nd challenge dose.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Saturated solution used for the intradermal injection induction procedure, 50% dilution in petrolatum used for the topical induction procedure, 5% dilution in petrolatum used for the 1st challenge dose and 1% dilution in petrolatum used for the 2nd challenge dose.

No. of animals per dose:

Treatment group of 10 and control group of 4

Details on study design:

RANGE FINDING TESTS:
Four patches at concentrations of 1, 5, 20 or 50% were applied to the shaved flanks of each of 4 guinea pigs and secured by an overlapping impermeable plastic adhesive tape and an elastic adhesive bandage which was wound around the torso of the animal and left in position for 24 hrs. The guinea pigs were pretreated with Freund’s adjuvant and petrolatum was used as the diluent. The skin sites were then evaluated 24 and 48 hrs after removal of the patch.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three pairs of simultaneous intradermal injections and one topical application
- Exposure period: patch test applied for 48 hrs, one week after the intradermal injections
- Test groups: one
- Control group: yes
- Site: clipped and closely shaved skin over the shoulder of the animal
- Frequency of applications: simultaneous intradermal injections followed 1 wk later by a 48-hr dermal application.
- Duration: 9 days
- Concentrations: 0.1 ml of a saturated solution of the test substance alone or 0.05 ml of the same test substance emulsified with adjuvant used in the intradermal injections, 50% dilution in petrolatum used in the topical application

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: two weeks after topical induction application
- Exposure period: 24 hrs
- Test groups: one
- Control group: yes
- Site: clipped skin on the flank
- Concentrations: 5% dilution in petrolatum used for 1st challenge phase and 1% dilution in petrolatum used for 2nd challenge phase 7 days later.
- Evaluation (hr after challenge): 24 and 48 hrs after removal of the patch

OTHER:
The topical application induction and challenge patches were secured by an overlapping impermeable plastic adhesive tape which, in turn, was secured by an elastic adhesive bandage wound around the torso of the animal.

Challenge controls:

The control group of guinea pigs was treated with sterile distilled water instead of the test material at induction. Otherwise the induction phase was identical, including the administration of Freund’s Adjuvant. The controls were challenged using the test substance in exactly the same manner as the test group of animals.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

None reported

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None reported.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 10.0. Total no. in groups: 10.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

4

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 4.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

4

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 4.0.

Results 5

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 10.0. Total no. in groups: 10.0.

Results 6

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 10.0. Total no. in groups: 10.0.

Results 7

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

1%

No. with + reactions:

0

Total no. in group:

4

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 4.0.

Results 8

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

1%

No. with + reactions:

0

Total no. in group:

4

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 4.0.

Any other information on results incl. tables

The results of the range-finding study indicated that a dilution of 5% could be used at the challenge phase without causing irritation.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

In a guideline GPMT, rhodium dicarbonyl acetylacetonate showed evidence of sensitization in all of the treated guinea pigs and, having a sensitization rate of 81-100%, would be classified as an extreme (grade 5) sensitizer on the Magnusson and Kligman Scale in this test system. Due to the method of test sample preparation, there is some doubt as to the identity of what was actually tested. On this basis, classification as category 1 is considered appropriate.

Executive summary:

The skin sensitising potential of rhodium dicarbonyl acetylacetonate was investigated in a study conducted according the method of Magnusson and Kligman (as described in OECD Test Guideline 406). The test item was administered, with and without Freund’s complete adjuvant, to the clipped skin over the shoulder of a group of ten female guinea pigs via intradermal injection ("saturated solution in water obtained by heating at 50 deg C for 24 hours, then cooled to ambient temperature"), followed one week later by a 48-hr topical application (occluded, 50% dilution in petrolatum) to the same clipped and shaved area. A 24-hr challenge dose (5% in petrolatum) was similarly applied 2 weeks after the topical induction to the clipped flank area and the site was evaluated 24 and 48 hrs after removal of the patch. The site was rechallenged with a 1% dilution in petrolatum and again assessed 24 and 48 hr after removal of the patch. A control group of 4 guinea pigs was similarly treated but without exposure to the test material at induction.

 

When challenged with both the 5 and 1% dilutions, all ten of the test animals exhibited positive reactions at the challenge site and no reactions were seen in any of the control animals. Rhodium dicarbonyl acetylacetonate was, therefore, classified as an extreme (grade 5) sensitizer, with a sensitization rate of 81-100%, in this test system.

 

Given the preparation method of the saturated solution for test induction, there is some doubt as to the identity of the substance actually tested. The substance exhibits solubility properties that indicate potential for decomposition that would be exacerbated by the conditions used to prepare the aqueous solution (stirring for 24 hours at 50 deg C). For this reason, there is currently considered to be insufficient information on the induction concentration and substance stability to determine a sub-category for skin sensitisation based on EU CLP criteria (EC 1272/2008). Classification as Category 1 is considered appropriate.