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Diss Factsheets

Administrative data

Description of key information

No data is available for skin irritation/corrosion or eye irritation on Hf substance ; read across with HfO2 and ZrO2 data is performed. Due to its inert property, the substance is neither a skin irritant, nor an eye irritant. These results are confirmed by different key studies.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted without any deviations to the guideline, but quoted with 2 because of the read across
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: in vitro test using human skin model
Details on test animals or test system and environmental conditions:
not applicable
Vehicle:
water
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 10 mg (26.3 mg/cm²) of the crushed powder were applied to the epidermis surface

VEHICLE: 5µL distilled water were used as vehicle
Details on study design:
The study was carried out with the Episkin SM tissues provided as a kit.
The tissues were exposed to the substance during 15 minutes and then post incubated 42h. The viability was determined by optical densimetry at 550nm to check the colouring potential of the substance (= reduction of MTT).
Irritation / corrosion parameter:
other: other: MTT reduction showed by optical density
Value:
98.4
Remarks on result:
other:
Remarks:
Basis: other: mean tissue viability. Reversibility: other: not applicable. (migrated information)
Irritant / corrosive response data:
The mean relative tissues viability is ≥ 50% and then substance showed no irritant effects.

table of results:

 

Negative control : PBS

Positive control : SDS 5%

HfO2

Blank corrected mean OD at 550nm

0.847

0.883

0.859

0.049

0.055

0.070

0.892

0.816

0.838

Blank corrected mean OD of the 3 replicates

0.863

0.058

0.849

Standard deviation OD

0.02

0.01

0.04

Relative tissue viabilities %

98.1

102.4

99.5

5.7

6.3

8.1

103.4

94.6

97.1

Mean tissue viabilities %

100

6.7

98.4

Standard deviation tissue viabilities %

2.2

1.3

4.6

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: UN GHS and EU CLP
Executive summary:

The potential of the test item to induce skin irritation was tested by using the three dimensional human skin model Episkin-SM. HfO2 was applied with water topically to the tissue for 15 minutes followed by a 42h post incubation period and immediate determination of cytotoxic effects via MTT reduction assay.

Irritant potential was predicted from the relative mean tissue viabilities obtained compared to the negative control treated with PBS.

HfO2 showed no irritant effects as the mean relative tissue viability was ≥ 50% (98.4%).

The controls confirmed the validity of the study:

- the mean optical density of the six blank values was < 0.1

- the mean absolute OD of the three negative control tissues was ≥0.6 and ≤ 1.5

- the mean relative tissue viability of the positive control (SDS 5%) was ≤ 40% (6.7%)

- the maximum standard deviation of viability of replicate tissues of all dose groups was ≤ 18% (1.3 - 4.5%).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented, scientifically sound study with methods similar to OECD guidline 405 with the following deviations: Not GLP, no information on environmental conditions, individual eye endpoints (cornea, iris, conjunctiva) were not reported in the results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Not GLP, no information on environmental conditions, individual eye endpoints (cornea, iris, conjunctiva) were not reported in the results.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Biotech Co., Ltd
- Age at study initiation: 4 months old
- Weight at study initiation: 3.22-3.59 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: no data To: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: right eyes were kept as controls
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): not aplicable


VEHICLE
- Amount(s) applied (volume or weight with unit): not aplicable
- Concentration (if solution): not aplicable
- Lot/batch no. (if required): not aplicable
- Purity: not aplicable
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3 animals (administered to the left eye of each animal)
Details on study design:
SCORING SYSTEM: according to Draize’s standard (1959); Cornea, iris and conjunctiva were observed, and acknowledged damages were recorded. After calculating the total scores of each observation of each animal (Individual ocular irritation index, IOI) and the average score of each observation of each group (Mean ocular irritation index, MOI), the evaluation was made according to the AFNOR (1982) evaluation criteria. The acute ocular irritation index (AOI) was defined as the maximum of the MOI.

Accident Value Test of Corneal Epithelium: After the accident value test of anterior ocular segment done 24 hours after the application, corneal epithelium were dyed with fluorescein, and the stainability was evaluated.


TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
other: MOI
Basis:
mean
Time point:
other: 48 hours
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: AOI
Basis:
mean
Time point:
other: 24 hours
Score:
6
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: Ocular reaction score
Basis:
mean
Time point:
other: 48 hours
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: MOI
Basis:
mean
Time point:
other: 24 hours
Score:
6
Max. score:
110
Reversibility:
fully reversible
Remarks:
72 hours
Irritation parameter:
other: MOI
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
110
Irritation parameter:
other: MOI
Basis:
mean
Time point:
other: 1 hour
Score:
4.7
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The AOI was determined to be 6.0 at 24 hours and the MOI after 48 hours was 2.0, therefore, this test agent was determined to be slightly irritating based on the AFNOR (1982) criteria. No irritation was observed after 72 hours.

The Accident Value Test of Corneal Epithelium 24 hours after application was zero in all three animals.
Other effects:
There were no abnormalities in the general condition or the weight changes to any of the 3 animals.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test agent was determined to be slightly irritating based on the AFNOR criteria. It does however not need to be classified for eye irritation according to the rules in the DSD and CLP.
Executive summary:

In this GLP study, performed according to the OECD 404 guideline,the test substance was determined to be slightly irritating based on the AFNOR criteria. Observed effects were fully reversible within 72 hours. It does however not need to be classified for eye irritation according to the rules in the DSD and CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

According to the REACh recommendations for the DNEL derivation (Guidance on information requirements and chemical safety assessment Chapter R.8: characterisation of dose (concentration)-response for human health), a read across could be used for substances with similar behaviour and toxic effects in the organism.

HfO2 and ZrO2 were used in a read across approach, for which the justification was developped in the toxicological headchapter summary.

  • skin irritation/corrosion

Four reliable studies are identified to assess the irritant potential of Hf. These studies are performed with Hf or with HfO2 and ZrO2 used for read across:

The first one showed the potential of HfO2 to induce skin irritation by using the three dimensional human skin model Episkin-SM, in a GLP study. HfO2 showed no irritant effects as the mean relative tissue viability was ≥ 50% (98.4%).

The second one, used wires containing 97 % Hf, as implant materials in Wistar rats. After 4 weeks of implantation, no inflammatory response was observed around the implants.

The two last ones, are GLP studies, performed according to the OECD 404 guideline, with New Zealand White rabbits exposed 4 hours to ZrO2 under an occlusive patch. No irritation, nor erythema, nor oedema were observed. The substance was hence determined not to be irritating to New Zealand White rabbit skin after 4 hours of exposure.

  • eye irritation

A reliable study was performed (Tosoh, 2000 – Klimisch 2) in New Zealand White rabbit. The test substance was ZrO2, used as read across, and was determined to be slightly irritating based on the AFNOR criteria. Observed effects were fully reversible within 72 hours.The slight irritation observed in the study performed with ZrO2, after 48 hours, is due to a mechanical action of the powder applied on the eyes.

 

Justification for classification or non-classification

Based on the available data, the substance was not classified under the CLP Regulation 1272/2008 nor the directive Classification and Labelling 67/548/EC.