Dimolybdenum carbide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1993-03-31 to 1996-01-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Sodium molybdate is used as read-across partner to Dimolybdenum carbide.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No data is available for Dimolybdenum carbide (target substance). Thus, available data from Sodium molybdate was used in a read-across approach. Due to a lower water solubility of Dimolybdenum carbide compared to Sodium molybdate the resulting bioavailability (toxicity potential) would also be expected to be lower. Therefore, the read across to the source substance Sodium molybdate is adequately protective. Details on the read-across rational are provided in section 13.

Test material

Test material information

Constituent 1

Reference substance name:

Sodium Molybdate 241/32

IUPAC Name:

Sodium Molybdate 241/32

Constituent 2

Reference substance name:

7631-95-0

Cas Number:

7631-95-0

IUPAC Name:

7631-95-0

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Sodium molybdate 241/32
- Physical state: white powder
- Analytical purity: 40.52% molybdenum, 19.29% sodium
- Purity test date: 1993-05-13
- Batch No.: 241/32
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 286 to 377 g
- Housing: in groups of 10 in suspended metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Induction:
- intradermal:
5 % w/w in water and
5 % w/w in a 50% mixture of Freund`s complete adjuvant and water for irrigation
- epicutaneous:
70 % w/w in water
Challenge:
- epicutaneous:
70% w/w in distilled water (applied to the anterior site) and 35 % w/w in water (applied to the posterior site)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Induction:
- intradermal:
5 % w/w in water and
5 % w/w in a 50% mixture of Freund`s complete adjuvant and water for irrigation
- epicutaneous:
70 % w/w in water
Challenge:
- epicutaneous:
70% w/w in distilled water (applied to the anterior site) and 35 % w/w in water (applied to the posterior site)

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS:
- 2 guinea-pigs
- Intradermal injection: 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0 % w/w sodium molybdate 241/32 in water and vehicle control
- Epicutaneous application: 30, 50, 60 and 70 % w/w sodium molybdate 241/32 in water

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1x intradermal, 1x epicutaneous
- Exposure period: 48 h of occlusive topical application
- Test groups: 1
- Control group: 2
- Site: 40 x 60 mm area of dorsal skin on the scapular region

Control and test animals were challenged topically two weeks after the topical induction

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: 20 x 20 mm patch applied to both anterior and posterior flank sides
- Concentrations: saturated Whatman No. 3 paper with 0.2 ml of Sodium molybdate 241/32 either 70 % (anterior) or 35 % (posterior) w/w in water
- Evaluation (hr after challenge): 24, 48 and 72 hours after removal of the patches

OTHER:
The preliminary investigations indicated, that topical application of 70 % w/w sodium molybdate 241/32 in water did not cause skin irritation. Therefore, six days after the intradermal injections, the same 40 x 60 mm area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.2 mL per site of 10 % w/w sodium lauryl sulphate in petrolatum. 24 hours later a 20 x40 mm patch of Whatman No. 3 paper was saturated with 0.4 mL of Sodium molybdate 241/32, 70% w/w in distilled water. The patch was placed on the skin under occlusive conditions and left in place for 48 hours.

Challenge controls:

Animals that were treated the same way like test animal for the procedure of induction wih the exception that the sodium molylbdate 241/32 was ommited. The challenge procedure was likewise to the test animals.

Positive control substance(s):

yes

Remarks:

formalin

Results and discussion

Positive control results:

Sensitivity of the guinea-pig strain used is checked periodically with formalin, a known sensitiser.
Formalin produced a clear positive response in all performed control experiments.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

70 and 35 % Sodium molybdate 241/32 w/w in water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 70 and 35 % Sodium molybdate 241/32 w/w in water. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

70 and 35 % of Sodium molybdate 241/32 w/w in water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 70 and 35 % of Sodium molybdate 241/32 w/w in water. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 3

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

70 and 35 % Sodium molybdate 241/32 w/w in water

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 70 and 35 % Sodium molybdate 241/32 w/w in water. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Any other information on results incl. tables

Clinical signs:

No signs of ill health or toxicity were recorded.

Induction:

- Intradermal injections: Necrosis was recorded at sites receiving Freund´s Complete Adjuvant in test and control animals.

A slight irritation was seen in test animals at sites receiving Sodium molybdate, 5% w/w in water for irrigation; no irritation was ovserved in the control animals reveiving water for irrigation.

- Topical application: Slight erythema was observed in test animals following topical application with Sodium molybdate 241/32, 70% w/w in distilled water. Very slight erythema was seen in the control guinea-pigs.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In conclusion, Sodium molybdate 241/32 is considered as not skin sensitising.

Executive summary:

In a dermal sensitization study (OECD 406) with Sodium molybdate in water, 20 young adult female guinea-pigs of the Dunkin-Hartley strain were tested using the method of Magnusson and Klingman. No dermal reactions were seen in a period of 72 hours after challenging the test animals.

In this study, Sodium molybdate is not a dermal sensitizer. Based on the results from the read-across partner, Dimolybdenum carbide is also expected not to be a dermal sensitizer.