Copper hydroxide nitrate (Cu2(OH)3(NO3))

Endpoint summary

Description of key information

Skin irritation: not irritating (OECD 404, GLP)
Eye irritation: severe irritant to the eye (OECD 405, GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from March 12, 2001 to March 16, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD).

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:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

hygiene: optimal hygienic conditions
room temperature: average of 20.3°C (continuous control and recording)
relative humidity: average of 50.8% (continuous control and recording)
air exchange: 12 per hour
light: artificial light from 6 a.m. to 6 p.m.
cages: individual caging in metal wire cages, type KK016R, with a wooden rest shelf
feed: Altromin 2023 diet for rabbits, ad libitum (producer: Altromin GmbH, D-32761 Lage) ; random samples of the feed are analysed for contaminants by Altromin ; Hay-briquettes (supplied by SSNIFF, D-59494 Soest) were offered additionally as a dietary supplement
water: tap water from an automatic watering system, ad libitum
identification: labelling with felt-tipped pen in a pinna
acclimatisation: 5 days

Type of coverage:

semiocclusive

Preparation of test site:

other: hair was clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after patch removal

Number of animals:

3 females

Details on study design:

Test substance administration:
Hair was clipped on the dorsal areas of the trunks one day before the application of the test substance. the test sites were median on the dorsal thoracal region.
Samples with approximately 0.5 g of the test substance were moistened with 1 mL deionised water and were placed on cellulose patches in a size of about 2.5 cm * 2.5 cm and were applied to the test sites. They were held in place by fixing them marginally with non irritating tapes. The application sies were covered semi-occlusively by a dressing.
Access by the animals to the application sites was prevented by a plastic collar.
At the end of the exposure period, the dressings, the tapes with the patches and the collars were removed, residual test substance was wiped off with wet Kleenex-tissues, if necessary.
Skin examinations:
The skins of the animals were examined for local alterations after the clipping procedure, one day before the application and immediately before application. the treated areas and the surrounding untreated skin (control area) of the animals were examined for erythema/eschar and oedema as well as for other local alterations approximately 1, 24, 48 and 72 hours after patch removal.
No further examinations were performed thereafter.
The skin was examined using a cold light source KL1500 electronic.
General examinations:
The animals were examined once daily for other than local changes of the skin.

Irritation parameter:

other: erythema/eschar score

Basis:

mean

Time point:

other: mean (24-72h)

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: mean (24-72h)

Score:

0

Max. score:

0

Other effects:

No general toxic effects were noted.

A light-blue staining of the skin at the application site was seen in all animals from 1h p.a. until a maximum of 24h after patch removal, but did not impede the xamination of the skin for erythema. The discoloration is directly attributed to a staining property of the test substance and not considered to be a toxic effect. Except for this, all exposed skin sites were normal at each examination term.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance Copper Hydroxide Nitrate is not irritating to the skin as per EU Regulations.

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:

experimental study

Adequacy of study:

key study

Study period:

from March 12, 2001 to April 03, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD)

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:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

hygiene: optimal hygienic conditions
room temperature: average of 20.3°C (continuous control and recording)
relative humidity: average of 51.6% (continuous control and recording)
air exchange: 12 per hour
light: artificial light from 6 a.m. to 6 p.m.
cages: individual caging in metal wire cages, type KK016R, with a wooden rest shelf
feed: Altromin 2023 diet for rabbits, ad libitum (producer: Altromin GmbH, D-32761 Lage) ; random samples of the feed are analysed for contaminants by Altromin ; Hay-briquettes (supplied by SSNIFF, D-59494 Soest) were offered additionally as a dietary supplement
water: tap water from an automatic watering system, ad libitum
identification: labelling with felt-tipped pen in a pinna
acclimatisation: 5 days

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

74 mg - approximated equivalent of 0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours p.a.

Number of animals or in vitro replicates:

1 female

Details on study design:

Additional eye examinations were performed 6, 8 10, 13 15 & 21 days after the instillation.
A further examination by instillation of a fluorescein solution (Minims Fluorescein Sodium 2%) onto the cornea was performed 48 hours p.a.
The whole eye, especially the cornea, the iris and the conjunctivae were examined, using a otoscope lamp.
In addition to the eye examinations, the animals were observed for other than local changes at all observation times too.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean (24-72h)

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: irreversible corneal alterations

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean (24-72h)

Score:

1

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean (24-72h)

Score:

2.7

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean (24-72h)

Score:

2.3

Max. score:

4

Other effects:

No other than ocular alterations were noted.

Cornea: Irreversible corneal alterations with scores of "2" were observed from 24 h to 72 h p.a. ; 6 d p.a. the score increased to "3". The affected area was one half to the whole cornea. Additionally a corneal neovascularisation, arising from the sclera was seen from 8 d to 21 d p.a. 75% of the cornea were homogeneously stained after an additional examintaion by instillation of fluorescein. This indicates a damage of the anterior corneal epithelium.

Iris: A sluggish reaction to the light (score "1") was noted from 24 h p.a. until 72 h p.a. From 6 d until 8 d p.a. no examinations were possible due to the corneal alterations. From 10 d until 21 d.p.a., the iris was normal.

Conjunctivae, redness: The animal was affected with scores ranging from "3" to "1", from 1 h p.a. onwards until a maximum of 10 d p.a.

Conjunctivae, chemosis: Swelling was noted from 1 h onwards until a maximum of 72 h p.a., starting with scores of "4" and afterwards decreasing.

Interpretation of results:

other: risk of serious damage to eyes.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test substance Copper Hydroxide Nitrate causes irreversible ocular lesions.
According to these results and to the EU CLP Regulation (n° 2008/1272), the test substance Copper Hydroxide Nitrate poses a "risk of serious damage to eyes".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation:

Reference Bernat (2001) is considered as the key study for skin irritation and will be used for classification. Results do not meet the criteria for classification (mean value ≥ 2.0 for one endpoint for all animals or for the 2 endpoints in at least 2 animals) according to regulation (EC) 1272/2008 as skin irritant, hence no classification required.

Eye irritation:

One reliable in-vivo study described by Bernat (2001) (OECD 405; GLP compliant) is considered to be reliable without restrictions. The substance was determined to be severely irritating to the eye.

Justification for selection of skin irritation / corrosion endpoint:
OECD test guideline

Justification for selection of eye irritation endpoint:
OECD test guideline

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation:

Skin irritation:

Reference Bernat (2001) is considered as the key study for skin irritation and will be used for classification. Results do not meet the criteria for classification according to regulation (EC) 1272/2008 as skin irritant, hence no classification required.

Eye irritation:

In-vivo study described by Bernat (2001) is considered to be reliable without restrictions. The substance was determined to be severely irritating to the eye.