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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from March 13, 2001 to March 29, 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class 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 22.5°C (continuous control and recording)
relative humidity: average of 49.9% (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forte, gamma irradiated with 25 kGy 60Co, ad libitum (producer: Altromin GmbH, D-32761 Lage) ; exception: the feed was withdrawn the evening before the administration of the test substance and was offered again about 3 hours afterwards ; random samples of the feed are analysed for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

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test substance was dissolved in deionised water.
The solutions were prepared freshly before administration and were administered within 10 minutes after the preparation.
A peroral administraiton was performed once in the morning by stomach intubation using a metal gavage.

Doses:

200 (male/female) & 2000 (male) mg per kg body weight
The dose volume was 20 mL 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:

3 (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.
Body weights were determined before administration, 7 days p.a., 14 days p.a., early deaths as soon as possible after fnding. Body weight gains were calculated for each week of the study, i.e. 0-7 days p.a. and 7-14 days p.a.
Deceased animals were dissected and examined macroscopically in an attempt to identify the target organs. Surviving animals were killed by CO2-asphyxia 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 - < 1 000 mg/kg bw

Mortality:

200 mg/kg b.w., males: all animals survived until the scheduled termination of the study.
200 mg/kg b.w., females: all animals survived until the scheduled termination of the study.
2000 mg/kg b.w., males: 2/3 animals died on the day of administration.

Clinical signs:

other: Only the high dose males were affected. The findings, with an onset shortly after administration and lasing until death or to a maximum of 10 d.p.a. were: - autonomous nervous effects: piloerection - central nervous effects: sedation - signs of discomfort

Gross pathology:

See 'Remarks on results' section.

Other findings:

Necropsy findings:
Anormal findings were present only in deceased animals: swelling of the gastric and intestinal mucosa, irritation of the trachea. tracheal irritation may be due to a minimum test substance reflux, but was not expressed enough to have been cause of death.
All other animalswere normal at the necropsy 14 d.p.a.

Any other information on results incl. tables

Synopsis of the results - time of death:

dose (mg/Kg)	sex	animal n°	nb. of animals			time of death
			exposed	affected	deceased
200	m	71 - 73	3	0	0	animals survived
200	f	76 - 78	3	0	0	animals survived
2000	m	81	3	3	2	between 2 and 4 hours
		82				animal survived
		83				between 2 and 4 hours

Body weights and body weight gains:

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.
200 mg/Kg    m	71	209	293	338	-	84	45
	72	206	264	288	-	58	24
	73	208	289	333	-	81	44
	mean	208	282	320	-	74	38
	SD	2	16	28	-	14	12
200 mg/Kg    f	76	168	195	200	-	27	5
	77	170	207	233	-	37	26
	78	180	229	246	-	49	17
	mean	173	210	226	-	38	16
	SD	6	17	24	-	11	11
2000 mg/Kg     m	81	213	a)	a)	-	a)	a)
	82	209	212	273	-	3	61
	83	221	a)	a)	-	a)	a)
	mean	214	-	-	-	-	-
	SD	6	-	-	-	-	-

a) animal died spontaneously.

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
Piloerection	2000, M	81 (a)	0,5h - 2h (b)	-
		82	0,5h - 1 d	-
		83 (a)	0,5h - 2h (b)	-
Closed eyes	2000, M	81 (a)	1h - 2h (b)	-
		83 (a)	1h - 2h (b)	-
Chromodacryorrhoea	2000, M	82	2d - 8d	low
Anaemia, pale skin	2000, M	82	6d - 9d	-
Hunched posture	2000, M	81 (a)	2h (b)	-
		82	6h - 10d	-
Sedation	2000, M	81 (a)	1 - 2h (b)	mid
		82	1h - 7 d	mid
		83 (a)	1 - 2h (b)	mid
Normal at any time	200, M	71	-	-
		72	-	-
		73	-	-
	200, F	76	-	-
		77	-	-
		78	-	-

(a) animal died spontaneously

(b) sign did not resolved before death

Necropsy findings:

Number of animals examined = 3 females and 6 males.

SYSTEM	Dose	Sex	N° of affected animals
organ, finding	(mg/kg)
normal	200	m	71, 72, 73
	200	f	76,77,78
	2000	m	82
ALIMENTARY SYSTEM
glandular stomach, mucosa, swelling	2000	m	81 (a), 83 (a)
intestinum, mucosa, swelling	2000	m	81 (a), 83 (a)
RESPIRATORY SYSTEM
trachea, local irritation	2000	m	81 (a)

(a) animal died spontaneously.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the oral LD50 for Basic Copper Nitrate was estimated to be higher than 500 and less than 1000 mg/ Kg bw in rats.
According to the EC Regulation No. 1272/2008 and subsequent regulations, Basic Copper Nitrate is classified as acutely toxic by oral route - category 4.