Mercury

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

1997-01-29 to 1997-03-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study, but reliable with restrictions - The study was conducted with an Ti-Hg, Cu-Sn Zr-Al alloy containing onla about 24.8% mercury. Minor deviations from the guideline: - A positive control group was missing in this study. - The concentration used for the induction phase should be the highest to cause mild irritation, but the concentration chosen caused no skin reaction. - Temperature range was 22 +/- 2 °C instead of 20 °C +/- 3°C. - Animals were not weighed at the end of the test. - The expiration date of the test item was not stated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

, 1992-07-17

Deviations:

yes

Remarks:

, please refer to "Rationale for reliability incl. deficiencies"

GLP compliance:

yes

Type of study:

Buehler test

Test material

Test material information

Constituent 1

Reference substance name:

Ti-Hg, Cu-Sn Zr-Al alloy

IUPAC Name:

Ti-Hg, Cu-Sn Zr-Al alloy

Details on test material:

- Name of test material (as cited in study report): MISCELA HY-TQS
- Chemical name: Ti-Hg, Cu-Sn Zr-Al alloy
- Chemical structure: N.A.
- Chemical class: alloys
- Physical state: grey powder
- Analytical purity: > 98 %
- Impurities: mainly oxygen
- Composition of test material, percentage of components: Ti 29.2 % - Hg 24.8 % - Cu 14.8 % - Sn 21.2- Zr 8.4 % - Al 1.6 %
- Batch No.: 01-96
- Preparation date: December 1996
- Stability: stable at room temperature
- Storage condition of test material: store in sealed vessel
- Known conditions that could lead to instability: heating above 100 °C may cause release of mercury vapours
No further information on the test material was stated.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A., Via Indipendenza, 11, 22050 Calco (Lecco) (Shipping slip No. 00404, dated January 7, 1997 and shipping slip No. 00974, dated February 7, 1997)
- Age at study initiation: about 6 weeks
- Weight at study initiation: between 416 and 492 g
- Housing: 2 or 3 animals/cage in air-conditioned room; Wire cages (40.5 x 38.5 x 18h) with a stainless steel feeder.
- Diet (ad libitum): Standard GLP diet - certificate coded 8 GP 22, produced by Charles River Italia's feed licensee Mucedola S.r.l., Settimo Milanese, was used. The diet was supplemented by the Producer with vitamins and trace elements.
- Water (ad libitum): filtered water
- Acclimation period: five days; animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2°C
- Relative humidity: 55 +/- 10 %
- Air changes: about 20/h filtered on HEPA 99.97 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Induction 2

Concentration / amount:

75 % (w/v) both in the induction phase and in the challenge application (Dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Challenge 2

Concentration / amount:

75 % (w/v) both in the induction phase and in the challenge application (Dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

No. of animals per dose:

Preliminary test: 2 male guinea pigs
Treatment group: 20 male guinea pigs
Control group: 10 male guinea pigs

Details on study design:

RANGE FINDING TESTS:
- The preliminary test was performed on a total of 2 animals in order to select the highest concentration that causes mild irritation to be used in the induction phase and the highest concentration that proves not to be irritating for the challenge exposure.
- Four concentrations, 75, 50, 25 and 12.5 % (w/v) were tested for the patch application.
- Each test article concentration was tested on 2 animals.
- An aliquot of each test article concentration was applied to the skin with a closed patch.
- Six hours after the administration, the patches were removed and the animals observed for up to 48 h for local reactions on the skin areas.
- All the concentrations used were well tolerated and not irritant.
- The highest concentration resulted in slight grey coloration which did not prevent skin evaluation.
- Therefore, the test article was used at the concentration of 75 % in the induction phase and for challenge exposure.

MAIN STUDY
- The test article MISCELA HY-TQS was suspended in paraffin oil (Batches No.s: 149 K 16870060 and 239 K 18423160; Expiry date: June and July, respectively 1997 (shelf life); Producer: Merck, Darmstadt (Germany)) to obtain a concentration of 75 % (w/v).
- The test article was ground in a mortar, mixed with a small amount of vehicle and then made up to volume while stirred.
- The test article formulates were prepared just prior to administration.

Induction phase:
- Day -1: an area of about 6 x 6 cm on the left flank of the animals of the treatment and control group was clipped with an electric clipper before treatment. Care was taken to avoid abrading the skin.
- Day 0: a filter paper (3M Whatman 2 x 3 cm) was fully-loaded with the test article or vehicle and applied to the skin areas clipped the day before. The patch was covered by an overlapping impermeable, hypoallergenic, plastic adhesive tape (3M Blenderm). This in turn was firmly secured by adhesive bandage (3M Micropore), wound around the torso of the animal. The dressing was left in place for 6 h.
- Days 7 and 14: the same application as on Day 0 was carried out on the same test area, clipped the day before treatment.

Challenge application:
- Day 27: an area of about 6 x 6 cm on the right flank of the animals of the two groups was clipped.
- Day 28: an occlusive patch (2 x 3 cm) loaded with the test article was applied to the posterior of the right flank of all animals, while the vehicle was applied analogously to the anterior of the flank. The patches were kept in contact for 6 h.
- Days 29 and 30: approximately 21 h after removing the patches the challenge areas were clipped and approximately 3 h later (about 30 h after application of the challenge patch) the skin was observed and any reaction recorded (day 29). Twenty-four hours after the above observation a second observation was made and again recorded (day 30).

OBSERVATION:
- For the evaluation of the skin reactions the Magnusson and Kligman grading scale was used.
- Observations of clinical signs were made daily.
- Body weight was recorded pre-trail and weekly thereafter.
- During the induction period, the skin was observed for irritant effects.
No further information on the study design was stated.

Challenge controls:

- Control group: paraffin oil (induction phase); 75 % (w/v) of test material (challenge period)
- 10 male guinea pigs were used for the vehicle control group.

Positive control substance(s):

no

Study design: in vivo (LLNA)

Statistics:

No data

Results and discussion

Positive control results:

No data

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No animal showed a positive reaction at the challenge.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No animal showed a positive reaction at the challenge..

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No animal showed a positive reaction at the challenge.

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No animal showed a positive reaction at the challenge..

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin reactivity was observed in the negative control group.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No skin reactivity was observed in the negative control group..

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin reactivity was observed in the negative control group.

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75 % (w/v) of the test item (dose administered: 225 mg/animal for each exposure (0.3 ml/patch). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No skin reactivity was observed in the negative control group..

Any other information on results incl. tables

- The body weight gain of the animals throughout the test was normal.

- Twenty-four hours after each treatment of the induction phase no reaction was observed in any of the animals.

- No animal showed a positive reaction at the challenge.

- No skin reactivity was observed in the negative control group.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

On the basis of the result, under the experimental conditions applied, MISCELA HY-TQS (containing about 24.8% mercury) did not appear to possess a sensitizing capacity.