Hafnium dioxide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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:

1999-03-08 to 1999-05-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented non GLP study similar to OECD guideline 406.

Qualifier:

according to guideline

Guideline:

other: Maximization Test of the Guideline for Toxicity Studies of Drugs (Notification No. 1-24 of Pharmaceuticals and Cosmetics Division dated September 11, 1989)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

not specified

Type of study:

other: Intradermal Sensitization-patch sensitization-elicitation

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Age at study initiation: 4 weeks old
- Weight at study initiation: 272 g - 302 g
- Housing: Five guinea pigs were kept together in each aluminum bracket cage (360 W x 520 D x 330 H mm, Bottom: 320 W x 480 D mm) until the elicitation treatment, then were kept individually in aluminum bracket cages (220 W x 380 D x 250 H mm) after the elicitation treatment. The cages were changed once a week.
- Diet: Solid feed (RC4, Oriental Yeast Col, Ltd)
- Water: Hita municipal water supply was used for water, which was provided freely by automatic water-supply equipments.
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/- 2 degree C
- Humidity (%): 55 +/- 15%
- Air changes (per hr): 10 ~ 15 ventilation per hour
- Photoperiod (hrs dark / hrs light): 12 hour light and dark period ( light on at 7 am- off at 7 pm)


IN-LIFE DATES: From: 1999-02-23 To: 1999-05-24

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

Intradermal sensitization
1) Test agent group

- E-FCA
- 2.5% test agent
- 2.5% test agent/FCA emulsion

2) Control group

- E-FCA

3) Positive control group

- E-FCA
- 0.1% DNCB/olive oil
- 0.1% DNCB/FCA emulsion

Patch sensitization
1) Test agent group
- 25% test agent
2) Control group
- 2.5 g of the test agent was suspended in “distilled injection water” to make 10 ml.
3) Positive control group
- 0.5% DNCB
Elicitation Treatment
1) Test group and control group
- 25% test agent
- 2.5% test agent
2) Positive control group
- 0.1% DNCB

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

Intradermal sensitization
1) Test agent group

- E-FCA
- 2.5% test agent
- 2.5% test agent/FCA emulsion

2) Control group

- E-FCA

3) Positive control group

- E-FCA
- 0.1% DNCB/olive oil
- 0.1% DNCB/FCA emulsion

Patch sensitization
1) Test agent group
- 25% test agent
2) Control group
- 2.5 g of the test agent was suspended in “distilled injection water” to make 10 ml.
3) Positive control group
- 0.5% DNCB
Elicitation Treatment
1) Test group and control group
- 25% test agent
- 2.5% test agent
2) Positive control group
- 0.1% DNCB

No. of animals per dose:

Control group: 5 animals
Test agent group: 10 animals
Positive conrol group: 5 animals

Details on study design:

Intradermal Sensitization:
Supra scapular fur was shaved by an electric clipper in order to establish 24 cm sensitization regions, and with the midline as the axis of symmetry, 0.1 ml of below preparations were injected per region of each left-right pair.
1) Test agent group
E-FCA
2.5% test agent
2.5% test agent/FCA emulsion
2) Control group
E-FCA (2 pairs in total)
3) Positive control group
E-FCA
0.1% DNCB/olive oil
0.1% DNCB/FCA emulsion

Patch Sensitization:
Six days after the intradermal sensitization, the fur in the sensitization regions of the animals in the control groups and the test agent group were shaved by an electric clipper and an electric shaver, then sodium lauryl sulfate (contains 10% petrolatum) was applied. Seven days after the intradermal sensitization, the control group were applied with “distilled injection water”, the test agent group with 25 % test agent, and the positive control group with 0.5 % DNCB, by placing 24 cm lints (Nankai Sangyou Co.) moistened with 0.2 ml each of the preparation on the shaved sensitization regions and by covering them with rubber dam sheets (Nihon Rikagaku Industry Co., Ltd.), then the trunks were wrapped with Dermicel (Johnson & Johnson K.K.) for 48 hours for occlusive dressing

Elicitation Treatment (challenge):
Fourteen days after the start of the patch sensitization, the flank fur of the animals were shaved by an electric clipper and an electric shaver, and for the control group and the test agent group, the areas were applied with 25% test agent and 2.5% test agent to each group, respectively, by placing 22 cm lints moistened with 0.1 ml of the preparation, and by covering them with oilpaper and rubber dam sheets, then the trunks were wrapped with Dermicel (Johnson & Johnson K.K.) for 24 hours for occlusive dressing. For the positive control group, 0.1% DNCB was applied by placing 22 cm lints moistened with 0.1 ml of the preparation and by covering them with rubber dam sheets, then the trunks were wrapped with Dermicel (Johnson & Johnson K.K.) for 24 hours for occlusive dressing

Challenge controls:

25% test agent
- 2.5 g of the test agent was suspended in “distilled injection water” to make 10 ml.
2.5% test agent
- 0.25 g of the test agent was suspended in “distilled injection water” to make 10 ml.
0.1% DNCB
- 0.01 g of DNCB was dissolved in ethanol to make 10 ml.

Positive control substance(s):

yes

Remarks:

E-FCA, 0.1% DNCB/olive oil; 0.1% DNCB/FCA emulsion

Positive control results:

0.1% DNCB elicited region: Diffused moderate erythema or severe erythema and edema were acknowledged in every sample 24 and 48 hours after the elicitation patch removal. Furthermore, scab formations were acknowledged in 4/5 cases after both 24 and 48 hours, and desquamation were acknowledged in all cases after 48 hours. The average scores 24 and 48 hours after the elicitation patch removal were 3.0 and 2.8, respectively.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

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. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

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. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Skin Reaction

2.1 Test Agent Group

1) 25% test agent elicited region.

No skin reaction was acknowledged 24 and 48 hours after the elicitation patch removal.

The average scores 24 and 48 hours after the elicitation patch removal were both 0.

2) 2.5% test agent elicited region

No skin reaction was acknowledged 24 and 48 hours after the elicitation patch removal.

The average scores 24 and 48 hours after the elicitation patch removal were both 0.

2.2 Control Group

1) 25% test agent elicited region.

No skin reaction was acknowledged 24 and 48 hours after the elicitation patch removal.

The average scores 24 and 48 hours after the elicitation patch removal were both 0.

2) 2.5% test agent elicited region

No skin reaction was acknowledged 24 and 48 hours after the elicitation patch removal.

The average scores 24 and 48 hours after the elicitation patch removal were both 0.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Since no skin reaction was acknowledged in the elicited region of either the test agent group or the control group, it was surmised that TZ-3y does not have skin sensitizing potential under the conditions of this test. On the other hand, it was confirmed that DNCB, the positive control agent, has an extreme skin sensitizing potential.

Executive summary:

The traditional skin sensitisation test was performed according to OECD guideline 406. Female Guinea pigs of the Hartley strain received following treatment:

Intradermal sensitisation

1) Test agent group - E-FCA (equal volume (v/v) of "distilled injection water" and Freund's complete adjuvant (FCA) were mixed and emulsified in water-in-oil style - 2.5% test agent - 2.5% test agent/FCA emulsion

2) Control group - E-FCA

3) Positive control group - E-FCA - 0.1% DNCB/olive oil - 0.1% DNCB/FCA emulsion

Patch sensitisation

1) Test agent group - 25% test agent

2) Control group - “distilled injection water”

3) Positive control group - 0.5% DNCB

Elicitation Treatment

1) Test group and control group - 25% test agent - 2.5% test agent

2) Positive control group - 0.1% DNCB

Zirconium dioxide was found to be not sensitising to the skin at level up to 25% whilst the positive control substance, DNCB, was found to have an extreme skin sensitising potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
No data is available on the sensitisation of hafnium dioxide. Based on the same behaviour, a read across with ZrO2 was performed. The substance is not a skin sensitisation substance.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Not required

Migrated from Short description of key information:
Not required

Justification for classification or non-classification

Based on the available data, the substance was not classified under the CLP Regulation 1272/2008 and the directive Classification and Labeling 67/548/EC.