Zirconium tetranitrate

Endpoint summary

Description of key information

skin irritation: not irritating to the intact rabbit skin (RCCA, 1986)
eye irritation: irreversible effects to the eye (RCCA, 1986)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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other: Non-GLP guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, Switzerland
- Age at study initiation: 14-15 weeks
- Weight at study initiation: 1.9-2.8 kg
- Housing: individually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet: pelleted standard Kliba 341, Batch 17/86 rabbit maintenance diet, ad libitum
- Water: community tap water from Itingen, ad libitum
- Acclimation period: 3 days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 (2 males, 1 female)

Details on study design:

TEST SITE
After approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimeters (10 x 10 cm). On test day 1, 0.5 ml of the test article was applied to the intact skin of the shaved area. It was covered with a 3 x 3 cm patch of surgical gauze. The gauze was covered with aluminium foil and then covered with an occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushing with luke warm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Maximum possible score: 4

No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (raised approximately 1 mm): 3
Severe edema (raised mode than 1 mm and extending beyond area of exposure): 4
Maximum possible score: 4

Maximum cumulative score: 8

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

Local signs (mean 1 hour to 72 hours) consisted of grade 0.0 erythema and grade 0.0 edema. In the area of application no staining of the treated skin by pigment or coloring of the test article was observed. No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other effects:

The body weight gain of all rabbits was similar. No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. Due to the results obtained, no macroscopic organ examination was indicated.

Interpretation of results:

not irritating

Remarks:

Migrated information

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: Non-GLP guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf, Switzerland
- Age at study initiation: 13-15 weeks
- Weight at study initiation: 2.2-2.7 kg
- Housing: individually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet: pelleted standard Kliba 341, Batch 17/86 rabbit maintenance diet, ad libitum
- Water: community tap water from Itingen, ad libitum
- Acclimation period: 3 days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as a negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

1, 24, 48 and 72 hours, 7, 14 and 21 days

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

1.7

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 + 48 + 72 hours

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

After 21 days, the substance still produced corneal opacity (whole area, from slight to severe) and visible vascularization in all 3 animals. Slight redness of conjunctiva (score 1) was still observed after 21 days in one animal.
In the area of application no staining of the cornea and conjunctivae by pigment or coloring of the test article was observed. No corrosion of the cornea was observed at any of the measuring intervals.

Other effects:

The body weight gain of all rabbits was similar. No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. Due to the results obtained, no macroscopic organ examination was indicated.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

General information

Water soluble zirconium salts like zirconium(tetra)nitrate, zirconium(di)acetate oxide or zirconium(tetra)acetate once in aqueous media dissociate very quickly at pH values of 4 to 9.5 forming the conjugate acid and hydrated forms of the insoluble ZrO2 (the most stable form of zirconium in water) (Daunderer, M.; Lehrbuch Klinische Toxikologie, 89. Erg. Lfg.; 11/94).

Due to the similar dissociation pattern it is concluded, that read across to other soluble zirconium salts is valid for the assessment of toxicological and ecotoxicological endpoints of zirconium(tetra)nitrate.

Tests with zirconium metal can be regarded as worst case scenario as dissociation of zirconium(tetra) nitrate will not lead to free zirconium metal in aqueous media.

Skin Irritation

A primary dermal irritation study according to OECD guideline 404 was conducted with zirconium di(acetate) oxide (RCCA, 1986). Three (2 males, 1 female) New Zealand White rabbits (14 - 15 weeks old weighing 1.9 - 2.8 kg) were dermally exposed to 0.5 mL of undiluted zirconium di(acetate) oxide for four hours under an occlusive dressing. Animals were then observed for 72 hours. Local signs (mean 1 hour to 72 hours) consisted of grade 0.0 erythema and grade 0.0 edema. In the area of application no staining of the treated skin by pigment or coloring of the test article was observed. No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Eye Irritation

In this primary eye irritation test, 0.1 mL of undiluted zirconium di(acetate) oxide was instilled into the conjunctival sac of three young adult New Zealand White rabbits (1 male, 2 females) (RCCA, 1986). The eye was not washed. Animals were observed for 21 days. Irritation was scored by the method of Draize et al.. After 21 days, the substance still produced corneal opacity (whole area, from slight to severe) and visible vascularization in all 3 animals. Slight redness of conjunctiva (score 1) was still observed after 21 days in one animal. In the area of application no staining of the cornea and conjunctivae by pigment or coloring of the test article was observed. No corrosion of the cornea was observed at any of the measuring intervals. Due to the irreversible effects on the cornea and conjunctiva the test substance needs to be regarded as severely irritating.

Justification for selection of skin irritation / corrosion endpoint:
Non-GLP guideline study, no restrictions, fully adequate for assessment.

Justification for selection of eye irritation endpoint:
Non-GLP guideline study, no restrictions, fully adequate for assessment.

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance needs to be classified and labelled as Xn, R41 "Risk of serious damage to eyes." under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EC. The test substance is not to be classified and labelled for skin irritation/corrosion.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance needs to be classified and labelled as eye damage cat. 1, H318 "Causes serious eye damage" under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC No 605/2014. The test substance is not to be classified and labelled for skin irritation/corrosion.