Cobalt wolframate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 July - 11 October 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cobalt wolframate

EC Number:

233-254-8

EC Name:

Cobalt wolframate

Cas Number:

10101-58-3

Molecular formula:

CoO4W

IUPAC Name:

cobalt wolframate

Details on test material:

Name: "COBALT WOLFRAMATE".
Trade name: Cobalt wolframate.
Chemical name: Cobalt wolframate.
Molecular formula: CoWO4.
Batch No.: 750702_20100329.
CAS No.: 10101-58-3.
Appearance: Fine grained dark-blue powder.
Purity: > 98%
Impurity: WO3 < 2 %
Solubility: Not soluble in water.
Conditions of storage: Room temperature.
Stability at conditions of storage: Stable.
Expiry date: 31 May 2015.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Species, strain: Rats, Crl:CD(SD).
Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.
Number and sex: 12 females.
Age: Between 8 and 12 weeks at the time of the administration.
Health conditions: A health inspection was performed prior to the commencement of treatment to ensure that the animals were in a good state of health.
Hygiene: Optimal hygienic conditions.
Room number: EH1-23.
Room temperature: Mean of 20.70 °C (continuous control and recording).
Relative humidity: Mean of 56.22 % (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 (37.5 cm x 21.5 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
Bedding material: Aspen wood chips, Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved. Random samples of the bedding material are analysed for contaminants by the supplier. Changes 1 / week.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week.
Feed: Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany. Analysis of the feed for ingredients and contaminants is performed randomly by Ssniff.
Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
Water: Tap water from an automatic watering system, ad libitum. Random samples of the water are analysed by the "AGES",
A-1226 Vienna, to check, if the water fulfils the requirements for drinking water for humans.
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: At least 7 days.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

deionised

Details on oral exposure:

Deionised water was used as vehicle for the test substance.
Justification: A homogeneous suspension could be prepared with water and water shall be used preferably, according to the guidelines.

The test substance was administered as a suspension.
The suspensions were prepared freshly before administration and were administered within 15 minutes after the preparation.

A peroral administration was performed once in the morning by stomach intubation using a metal gavage.
The dose volume was 10 mL per kg body weight. The individual dose volumes were calculated using the body weights determined on the day of the administration.

Test procedure
Annex 2c of the OECD guideline and Annex 1c of the EC-Directive were used for the stepwise dosing to groups of 3 females each.
The sequence of dosing of the test substance was:
• Step 1: 300 mg per kg body weight.
• Step 2: 300 mg per kg body weight.
• Step 3: 2000 mg per kg body weight.
• Step 4: 2000 mg per kg body weight.

Justification for the selection of the dose
As no prior information on the toxicity of the test substance was available, a starting dose of 300 mg of the test substance per kg body weight was chosen. The further proceeding was in accordance with the guideline/directive.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Clinical observations
Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 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 occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.

Body weights and body weight gain
Body weights were determined
• before administration.
• 7 days p.a.
• 14 days p.a.
Body weight gain was calculated for each week of the study, i.e. between
• 0 and 7 days p.a.
• 7 and 14 days p.a.

The animals were sacrificed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Statistics:

None

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals did not show any clinical signs during the entire observation period.

Gross pathology:

No abnormal findings were made in all animals at the necropsy 14 d p.a.

Other findings:

None

Any other information on results incl. tables

Synopsis of the results

Dose	Step No.	Animal	Number of animals
(mg/kg)		Nos.	exposed	affected	deceased
300	1	11, 12, 13	3	0	0
300	2	14, 15, 16	3	0	0
2000	3	21, 22, 23	3	0	0
2000	4	24, 25, 26	3	0	0

Body weights and body weight gain

Individual data, means and standard deviations SD.

Dose	Animal	Body weight (g)			Body weight gain (g)
mg/kg (Step No.)	No.	before administr.	7 days p.a.	14 days p.a.	death	0-7 days p.a.	7-14 days p.a.
300	11	182	219	231	-	37	12
(1)	12	189	229	247	-	40	18
	13	193	219	221	-	26	2
	mean	188.0	222.3	233.0	-	34.3	10.7
	SD	5.6	5.8	13.1	-	7.4	8.1
300	14	220	261	280	-	41	19
(2)	15	197	232	257	-	35	25
	16	194	236	240	-	42	4
	mean	203.7	243.0	259.0	-	39.3	16.0
	SD	14.2	15.7	20.1	-	3.8	10.8
2000	21	179	215	231	-	36	16
(3)	22	177	214	230	-	37	16
	23	175	215	241	-	40	26
	mean	177.0	214.7	234.0	-	37.7	19.3
	SD	2.0	0.6	6.1	-	2.1	5.8
2000	24	196	221	223	-	25	2
(4)	25	185	205	224	-	20	19
	26	191	222	235	-	31	13
	mean	190.7	216.0	227.3	-	25.3	11.3
	SD	5.5	9.5	6.7	-	5.5	8.6

Observations in life

Findings	Dose (mg/kg), Step No.	Animal Nos.	Observation time (p.a.) first    last
no clinical signs	300, 1	11, 12, 13	0 h / 14 d
	300, 2	14, 15, 16	0 h / 14 d
	2000, 3	21, 22, 23	0 h / 14 d
	2000, 4	24, 25, 26	0 h / 14 d

Necropsy findings

Number of animals examined: 12 females.

SYSTEM Organ, finding	Dose (mg/kg)	Step No.	Animal Nos.
no abnormal findings	300	1	11, 12, 13
	300	2	14, 15, 16
	2000	3	21, 22, 23
	2000	4	24, 25, 26

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No toxic effects of the test substance were noted by signs in life and post mortem at a dose of 2000 mg test substance per kg body weight. No mortality occurred.
According to Commission Directive 2001/59/EC "COBALT WOLFRAMATE" does not require classification for acute oral toxicity.

Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance after a single peroral administration to rats.

Methods

Methods and investigations were performed in conformance with the OECD-Guideline 423, 17 December 2001 and theCouncil Regulation (EC) No 440/2008,Method B.1 tris.

Administration of the test substance

"COBALT WOLFRAMATE"was administered once orally via gavage as a suspension in deionised water to female Crl:CD(SD) rats.

The dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg per kg body weight and 2000 mg per kg body weight as the second dose.

The dose volume was 10 mL per kg body weight for all groups.

Investigations

·      Body weights: before administration, 7 and 14 days after the administration (p.a.).

·      Clinical observations: at least once per day.

Necropsy: The animals were sacrificed and necropsied 14 days p.a.

Results

Dose (mg/kg)	Step No.	No. of animals			Prominent findings
		exposed	affected	deceased	in life	post mortem
300	1	3	0	0	none	none
300	2	3	0	0	none	none
2000	3	3	0	0	none	none
2000	4	3	0	0	none	none

 

Presence of signs in life	no signs
Full recovery of the animals	not applicable
Body weights	all animals gained weight in both weeks p.a.
Findings in life and post mortem indicate	no toxic effects present
LD50, oralaccording to OECD	> 5000 mg/kg body weight

Conclusion

According to Commission Directive 2001/59/EC"COBALTWOLFRAMATE"does not require classification for acute oral toxicity.