Hexakis[μ-(acetato-O:O')]-μ3-oxo-triangulo-triruthenium acetate

Endpoint summary

Description of key information

In a guideline in vivo guinea pig maximisation test (GPMT), to GLP, ruthenium acetate exhibited mild sensitising potential, but did not meet the EU criteria for classification as a skin sensitiser (Allen, 1996).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20-Nov-1995 to 25-Dec-1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 406)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study conducted in 1996

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Ltd, Burton-on-Trent, Staffordshire, UK

- Age at study initiation: 8-12 weeks

- Weight at study initiation: 380-431 g

- Housing: singly or in pairs in solid-floor polypropylene cages furnished with woodflakes

- Diet (e.g. ad libitum): Guinea pig FD1 diet, ad libitum

- Water (e.g. ad libitum): mains tap water, ad libitum

- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22

- Humidity (%): 47-60

- Air changes (per hr): ~15

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

IN-LIFE DATES: From: 20-Nov-1995 To: 25-Dec-1995

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Intradermal induction: 0.05% w/v in water, 0.05% w/v in Freund's Complete Adjuvant:water (1:1)
Topical induction: 50% w/v in water
Topical challenge: 25% and 10% in water

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Intradermal induction: 0.05% w/v in water, 0.05% w/v in Freund's Complete Adjuvant:water (1:1)
Topical induction: 50% w/v in water
Topical challenge: 25% and 10% in water

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS:
For intradermal induction:
- Test material concentrations: 0.01, 0.05, 0.1, 0.5, 1 and 5%
- Vehicle: water
- No. animals/concentration: 1
- Injection volume: 0.1 ml
- Timepoints for assessment: 24, 48 and 72 hours and 8 days after injection
- Evaluation parameters: erythema using Draize scale, systemic toxicity
- Interpretation criteria: highest concentration that caused mild/moderate skin irritation and well tolerated systemically selected for main study
- Results: selected concentration 0.05%

For topical induction:
- Preparation of animals: intradermal injection with Freund's Complete Adjuvant (FCA) 18 days previously
- Test material concentrations: 5, 10, 25 and 50%
- Vehicle: water
- No. animals: 2, each treated with 4 concentrations
- Conditions of exposure: occlusive, 48 hours
- Timepoints for assessment: 1, 24 and 48 hours after end of exposure
- Evaluation parameters: erythema and oedema
- Interpretation criteria: highest concentration that caused mild/moderate skin irritation selected for main study
- Results: selected concentration 50%

For topical challenge:
- Preparation of animals: as for control animals in main study up to day 14
- Test material concentrations: 5, 10, 25 and 50%
- Vehicle: water
- No. animals: 2, each treated with 4 concentrations
- Timepoints for assessment: 1, 24 and 48 hours after end of exposure
- Interpretation criteria: highest non-irritant concentration selected for main study
- Results: selected concentrations 25 and 10%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, 1 intradermal, 1 topical

- Exposure period: 48 hours (topical)

- Test groups: 1 group of 10 animals

- Control group: 1 group of 5 animals

- Site: shoulder, hair clipped from an area ~4 cm x ~6 cm

- Frequency of applications: weekly (intradermal on study day 0, topical on study day 7)

- Duration: not applicable (details of exposure as above)

- Concentrations:
- Intradermal injection at 3 sites: a) FCA: water (1:1), b) 0.05% test material in water, c) 0.05% test material in FCA: water (1:1)
- Topical application across same sites: 50% test material in water (v/v) applied on filter paper ~4 cm x ~ 2 cm
- Similarly for control animals with the omission of the test material

B. CHALLENGE EXPOSURE
- No. of exposures: 1

- Day(s) of challenge: Study day 21

- Exposure period: 24 hours

- Test groups: 1 group of 10 animals, each tested with 25% and 10%

- Control group: 1 group of 5 animals, each tested with 25% and 10%

- Site: flank (right 25%, left 10%)

- Concentrations: 25% and 10% in water (applied on filter paper ~2 cm x ~2 cm)

- Evaluation (hr after challenge): 24 and 48 hours

OTHER:
- Body weight: recorded on day 0 and 24 of the main study

Challenge controls:

5

Positive control substance(s):

yes

Remarks:

historical data, various substances

Positive control results:

In 5 studies performed at the testing laboratory between March 1994 and August 1995, the incidence of skin sensitisation with the positive control material ranged from 39 to 100%; the positive control materials used were 2-mercaptobenzothiazole, ethyl 4-aminobenzoate, 2,4-dinitrochlorobenzene and neomycin sulphate

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Body weight gains were comparable in the test and control groups over the 24-day period of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline in vivo guinea pig maximisation test (GPMT), to GLP, ruthenium acetate exhibited mild sensitising potential, but did not meet the EU criteria for classification as a skin sensitiser.

Executive summary:

The skin sensitisation potential of ruthenium acetate was evaluated in a guinea pig maximisation test (GPMT), conducted according to OECD guideline 406, and to GLP. Following sighting tests to establish appropriate induction and challenge doses, a group of 15 guinea pigs (10 test and 5 control) was used for the main study. Intradermal induction with the test material at 0.05% in water (with and without Freund's Complete Adjuvant) was followed 1 week later by a 48-hour topical induction with the test material at 50% in water; controls received vehicle only. Challenge doses of 10 and 25% (in water) were applied (for 24-hr) to all test and control animals on day 21, and the skin was evaluated 24 and 48 hr later.

 

A single animal showed a reaction to the 25% challenge concentration at both time points; there were no reactions at the 10% challenge, or in controls at either time point. The test substance gave a 10% sensitisation response at the challenge concentration of 25%, making it a mild sensitiser.

 

Since a 30% sensitisation response is required for classification under EU CLP criteria (EC 1272/2008), the test substance is not classified as a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No relevant human sensitisation data were identified.

 

The skin sensitisation potential of ruthenium acetate was evaluated in a guinea pig maximisation test (GPMT), conducted according to OECD guideline 406, and to GLP. Following sighting tests to establish appropriate induction and challenge doses, a group of 15 guinea pigs (10 test and 5 control) was used for the main study. Intradermal induction with the test material at 0.05% in water (with and without Freund's Complete Adjuvant) was followed 1 week later by a 48-hour topical induction with the test material at 50% in water; controls received vehicle only. Challenge doses of 10 and 25% (in water) were applied (for 24-hr) to all test and control animals on day 21, and the skin was evaluated 24 and 48 hr later. A single animal showed a reaction to the 25% challenge concentration at both time points; there were no reactions at the 10% challenge, or in controls at either time point. The test substance gave a 10% sensitisation response at the challenge concentration of 25%, making it a mild sensitiser (Allen, 1996). However, since a 30% sensitisation response is required for classification under EU CLP criteria (EC 1272/2008), the test substance is not classified as a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No respiratory tract sensitisation data are available. A new study was not conducted as no standard and validated test method is available and it is not a REACH Standard Information Requirement. 

Justification for classification or non-classification

Based on the results of the available and reliable GPMT, hexakis[mu-(acetato-O:O')]-μ3-oxo-triangulo-triruthenium acetate / ruthenium acetate does not require classification as a skin sensitiser according to EU CLP criteria (EC 1272/2008).