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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from March 13, 2001 to April 10, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

439-590-3

EC Name:

-

Cas Number:

12158-75-7

Molecular formula:

Cu2H3NO6

IUPAC Name:

copper(2+) hydroxide nitrate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

batch n°: 060248
composition of the test material: Cu=52.6% - N=5.4% - H=1.5% - O=36.8%
solubility in water: practically insoluble
expiration date of the batch: February 2002
storage conditions of test substance: ambient temperature

Test animals

Species:

rat

Strain:

other: Crl: CD (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

hygiene: optimal hygienic conditions
room temperature: average of 21.6°C (continuous control and recording)
relative humidity: average of 62.4% (continuous control and recording)
air exchange: 12 per hour
light: artificial light from 6 a.m. to 6 p.m.
cages: single caging in Makrolon cages type III ; wire mesh lids ; sanitation of cages once a week
bedding material: aspen wood chips, type "4 HV", autoclaved ; the bedding material was changed weekly
environmental enrichment: nibbling wood bricks and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week
feed: Altromin 1324 forte, gamma irradiated with 25 kGy 60Co, ad libitum (producer: Altromin GmbH, D-32761 Lage) ; random samples of the feed are analysed for contaminants by Altromin
water: tap water from an automatic watering system, ad libitum
identification: labelling with felt-tipped pen on the tail and on the cage
acclimatisation: at least 5 days

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: soaked with deionised water

Details on dermal exposure:

Hair of the dorsal trunk was clipped with an electrical hair clipper one day before the application of the test substance. The test site was located on the median dorsal thoracal region.
A dermal administration was performed once by spreading the test substance on an area of about 10% of the estimated body surface. An area of 5 cm x 6 cm was labelled in a relaxed animal. This area, when stretched for administration, gives an application site of about 50 cm².
A cellulose patch with the calculated amount of the test substance, spread over an area of approximately 5 cm x 6 cm and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape. Patch and tape were covered semi-occlusively by a dressing.
At the end of the exposure period, the dressing, the tape and the patch were removed. Residual test substance was wopped off using a cellulose tissue.

Duration of exposure:

24 hours

Doses:

2000 (male/female) mg per kg body weight
The individual dose volumes were calculating using the body weights determined at the day of administration.

No. of animals per sex per dose:

5 (in dose groups)

Control animals:

no

Details on study design:

Observations were performed within the periods 0-0.5, 0.5-1, 2-4 and 4-6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurence of secretions and excretions, automatic activity, changes in gait, posture and the presence of convulsions.

Results and discussion

Preliminary study:

In a range finding study 3 groups of one male and one female each were dosed with 400 or 894 or 2000 mg per kg body weight. All animals survived until 7d.p.a. Therefore a limit test with one dose of 2000 mg per kg body weight was performed.
Both animals, dosed with 2000 mg/kg body weight in the preliminary test, were included into the main study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were affected. The findings in life were: - signs of discomfort: chromodacryorrhoea - other effects: staining of the skin at the application site ; This discoloration is directly attributed to a staining property of the test substance ans is n

Gross pathology:

See 'Remarks on results' section.

Other findings:

Necropsy findings:
No abnormal findings were made post mortem.

Any other information on results incl. tables

Synopsis of the results:

Main study:

Sex	Animal n°	Dose (mg/Kg)	Number of animals
			exposed	affected	deceased
m	321-325	2000	5	5	0
f	326-330	2000	5	5	0

Range finding study:

Sex	Animal n°	Dose (mg/Kg)	Number of animals
			exposed	affected	deceased
m	301	400	1	1	0
f	306	400	1	1	0
m	311	894	1	1	0
f	316	894	1	1	0
m	321	2000	1	1	0
f	326	2000	1	1	0

Body weight and body weight gain:

Dose	Animal n°	Body weight (g)				Body weight gain (g)
Sex		before administration	7 days p.a.	14 days p.a.	death	0-7 days p.a.	7-14 days p.a.
200o mg/Kg    m	321	294	322	356	-	28	34
	322	271	317	369	-	46	52
	323	278	330	378	-	52	48
	324	292	332	380	-	40	48
	325	293	347	391	-	54	44
	mean	286	330	375	-	44	45
	SD	10	11	13	-	10	7
2000 mg/Kg    m	326	253	254	279	-	1	25
	327	231	234	246	-	3	12
	328	236	239	245	-	3	6
	329	228	230	248	-	2	18
	330	234	252	261	-	18	9
	mean	236	242	256	-	5	14
	SD	10	11	14	-	7	8

Observations in life:

'low-mid-high': grade of severity was recorded (where applicable).

'-': no grade of severity applicable.

Findings	Dose (mg/Kg), sex	N° of affected animals	Observation time (p.a.) first - last	Maximum grade of severity
Chromodacryorrhoea	2000, M	321	6h - 1d	low
	2000, F	327	0,5h - 6h	low
Test substance related stain of skin	2000, M	321	1d - 3d	-
		322	1d - 3d	-
		323	1d - 4d	-
		324	1d - 3d	-
		325	1d - 4d	-
	2000, F	326	1d - 4d	-
		327	1d - 3d	-
		328	1d - 2d	-
		329	1d - 3d	-
		330	1d - 2d	-

Necropsy findings:

Number of animals examined: 5 males and 5 females

SYSTEM	Dose	Sex	N° of affected animals
organ, finding	(mg/kg)
normal	2000	m	321, 322, 323, 324, 325
	2000	f	326, 327, 328, 329, 330

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the dermal LD50 for Basic Copper Nitrate was estimated to be higher than 2000 mg/ Kg bw in rats.
According to the EC Regulation No. 1272/2008 and subsequent regulations, Basic Copper Nitrate is not classified as acutely toxic by dermal route.