Copper

Endpoint summary

Description of key information

Several high quality criteria studies  (reliability 1 or 2) on several copper compounds and copper are available from the VRAR (2008).  Studies on coated copper flakes and CuO were retained.
The VRAR, 2008 provides additional lower quality studies as well as studies specific to other soluble copper compounds.  If not pivotal to this copper REACH dossier, they are described in the copper VRAR (2008) but not further discussed  in this CSR.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

in vivo for skin irritation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD guideline 404 and EU method B.4 The test material has no batch number and no information on purity nor particle size distribution.

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:

source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
At the start of the study the animals weighed 2.77 to 3.08 kg and were 12 to 16 weeks old.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: distilled water

Controls:

no

Amount / concentration applied:

concentration in vehicle: 50% w/v
total volume applied: ca. 1ml

Duration of treatment / exposure:

4h

Observation period:

72h

Number of animals:

3: 2 females and 1 male

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72

Score:

0

Max. score:

0

Reversibility:

other: not relevant. no skin irritation was noted in this study

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material corresponds to the composition of “ copper coated flakes” .
A single 4hr, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation.

Executive summary:

The test material identity was not provided in details. Considering the information from the reports on the same material, the tested material falls in the composition category of "coated copper flakes", consistent with a biocidal product use (PBD notification was the reason for doing the test).

A single 4hr, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation.

In this study, copper powder does not meet the criteria for classification for dermal irritation according to Annex VI of Commission Directive 2001/59/EC

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

in vivo for eye irritation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD Guideline 405 and EU Method B.5 The test material has no batch number and no information on purity nor particle size distribution.

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:

Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
At the start of the study the animals weighed 2.0 to 3.5 kg and were 12 to 16 weeks old.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL (approximately 72 mg).

Duration of treatment / exposure:

the test material was placed into the conjuctival sac of the right eye. The upper and lower lids were held together for ca. 1 second after treatment.
Apparently eyes were not rinsed.

Observation period (in vivo):

Up to 14 days

Number of animals or in vitro replicates:

3 per group (females)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72h

Score:

0

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72h

Score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72h

Score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72h

Score:

0

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72h

Score:

0.7

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72h

Score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72h

Score:

1.7

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72h

Score:

1.7

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72h

Score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72h

Score:

0.7

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72h

Score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72h

Score:

1.7

Reversibility:

fully reversible within: 14 days

Other effects:

Clinical signs: copper-coloured staining of the eyelids and fur around the treated eye was noted in all animals during the study

Interpretation of results:

slightly irritating

Remarks:

Migrated information however, not classified Criteria used for interpretation of results: EU

Conclusions:

Good quality study. The test material corresponds to the composition of “ coated copper flakes” . In this study the test material showed a slight potential to induce eye irritation. However, the material does not meet the criteria for classification for eye irritation according to Annex VI of Commission Directive 2001/59/EC

Executive summary:

The test material corresponds to the composition of “coated copper flakes” . In this study the test material showed a slight potential to induce eye irritation. However, the material does not meet the criteria for classification for eye irritation according to Annex VI of Commission Directive 2001/59/EC

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

With regard to skin irritation, available animal data for copper (II) oxide and coated copper flakes do not require these substances to be classified as irritant. Considering the lower solubility and bioaccessability of copper powders compared to copper oxides and copper flakes, the data are read-across to (powders and massive forms) do not require classification for skin irritation.

With regard to eye irritation, available animal data for copper (II) oxide and coated copper powder indicated some slight eye irritation for the coated copper flakes but only the latter do require classification as irritant.  Considering the lower solubility and bioaccessibility of copper powders compared to copper oxides and copper flakes, and the differences in shapes, no classification is proposed for copper powders.

Justification for selection of skin irritation / corrosion endpoint:
Several studies are used in WoE.
The studies, retained in weight of evidence approach, were evaluated by the competent authorities on existing substances and biocides

Justification for selection of eye irritation endpoint:
Several studies used in WoE.
The studies, retained in weight of evidence approach, were evaluated by competent authorities on existing substances and biocides.

Justification for classification or non-classification

Justification for classification/non classification:

RAC 2014 opinion on Sanders (2001d) for Coated copper flakes concludes on a mean scores per animal over the 24/48/72h time period are reported in the table below.

 

	Cornealopacity	Iritis	Conjunctivalredness	Conjunctivalchemosis
Animal#1 Animal#2 Animal#3	0 1 2	0 0.67 1	1.67 1.67 2	0.67 1 1.67

 

 

The eye of animal#1 appeared normal on day7, the eyes of animals#2 and 3 on day14.By averaging the individual scores for all animals together,the dossier submitter arrived at mean scores of 1, 0.57, 1.8 and 1.13 for corneal opacity, iritis, conjunctivalredness and chemosis, respectively,and concluded that these were below the values requiring classification.

 

Coated copper flakes caused signs of irritation in the available eye irritation study. All effects were shown to be reversible within 21 days. Whereas the mean scores over 24-72 h were below the threshold values for classification for iritis, conjunctival redness and chemosis (≥1, ≥2 and ≥2, respectively), the mean score for corneal opacity over 24-72 h was at or above the threshold value for classification (≥1) in 2 of the 3 tested animals. The mean score over all three animals (1) was also at this threshold value. RAC therefore concludes that coated copper flakes fulfilled the criteria for classification and that it should therefore be classified as Eye Irrit. 2 – H319.

 

For copper (II) oxide, RAC 2014 concluded that there was no need for classification.

Copper powders differ from coated copper flakes on basis of their (bio availability) solubility pattern and their shapes (ie no blade-type edages) than coated copper flakes. No classification for copper powder is therefore proposed.