Aluminum cobalt oxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given but only males were tested, only one dose level, no detailed clinical observation, limited parameters examined, no data on test substance purity.

Data source

Reference

Reference Type:

publication

Title:

A study of the effects of cobalt administered orally to rats; Short title: Semichronic oral cobalt toxitcity in rats

Author:

Domingo, J.L. et al.

Year:

1984

Bibliographic source:

Arch. de Farmacol. y Toxicol. X: 13-20

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

(40 animals/group, only males tested, only one dose tested, limited parameters examined, no detailed clinical observation)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cobalt (II) chloride

IUPAC Name:

Cobalt (II) chloride

Details on test material:

Name of test material (as cited in study report): Cobaltous chloride (not specified if hexahydrate or not)
Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 80 g
- Housing: in Macrolon cages; 10 of each group in individual cages stainless steel to study their metabolism
- Diet: perfectly balanced PANLAB diet; ad libitum
- Water: drinking water; ad libitum

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

The selection of the concentration of 500 ppm was made on the basis of the data obtained in a previous study lasting one month.

Duration of treatment / exposure:

3 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
500 ppm
Basis:
nominal in water

No. of animals per sex per dose:

40 males

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: based on a previous study

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: twice weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: every 2 weeks
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 4/group
- Parameters examined: haematocrit, and haemoglobin

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: every 2 weeks
- Animals fasted: No data
- How many animals: 4/group
- Parameters examined: glucose, urea, total proteins, cholesterol, uric acid, creatinine, alkaline phophatase, GOT, and GPT

URINALYSIS: Yes
- Time schedule for collection of urine: daily
- Metabolism cages used for collection of urine: Yes (10 animals per group)
- Animals fasted: No data
- Parameters examined: No data

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: The Protein Efficiency Coefficients (PEC) were determined every 2 weeks. (PEC is defined as a quotient between the weight gain and the nitrogen ingested.)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes; organ weights: liver, kidneys, spleen, heart, lungs, and testicles (all animals)
HISTOPATHOLOGY: Yes; heart, kidney, liver, suprarenals, spleen, stomach, pancrease, duodenum, colon, skeletal muscle, lung, and testicle (3 animals per group); an ultrastructural study was made of samples of the right and left ventricle including the endocardium

Other examinations:

In liver, kidneys, spleen, heart, lungs, testicles, and in the abdominal muscle, the concentration of accumulated cobalt was determined by readings from an atomic absorption spectrophotometer. At the end of the experiment also the blood was analysed for cobalt accumulation.

Statistics:

Student-Fischer t-test

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No data

BODY WEIGHT AND WEIGHT GAIN
The treated animals' growth was significantly less (P < 0.001) than the control rats in the first 6 weeks; i.e. during the period in which the weight increase is considerable. From the 2nd month, the variations between both groups are no longer significant.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The quantities of nitrogen ingested fortnightly, are significantly different from the 2nd fortnight (P < 0.01) to the 4th (P < 0.001); this does not exist in the 3rd month.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
The drinking water ingested was significantly less (P < 0.001) for the treated animals after the 2nd fortnight.

HAEMATOLOGY
Significant increases were seen in the haematocrit (P < 0.001) and in the haemoglobin (P < 0.001) over the whole study period.

CLINICAL CHEMISTRY
No significant differences were observed.

URINALYSIS
The volume of urine excreted was significantly less (P < 0.001) for the treated rats than for the controls.

ORGAN WEIGHTS
Changes in organ weights were observed in the lungs (significant increase, P < 0.01). Hypertrophy of the spleen was observed (P < 0.001).

GROSS PATHOLOGY
No data

HISTOPATHOLOGY: NON-NEOPLASTIC
No morphological changes or atypical intracellular deposits were noted in any of the samples obtained and examined, nor were there any relevant ultrastructural irregularities.

OTHER FINDINGS
The accumulated cobalt values for rats during the three months period show an increase of the metal in all the organs analyzed, although it was only significant in the heart in and the spleen (P < 0.01) and particularly in the kidneys and liver (P < 0.001).

Effect levels

Dose descriptor:

LOAEL

Effect level:

500 other: ppm (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: organ weights, body weight gain, drinking volume, haematological parameters

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Organ weights

Organ	Control: organ weight [g]	Test group: organ weight [g]	Deviation [%]
Liver	3.12 ± 0.33	3.22 ± 0.24	+ 3.21
Kidneys	0.73 ± 0.69	0.68 ± 0.078	- 6.85
Spleen	0.14 ± 0.19	0.20 ± 0.018	+ 42.86***
Heart	0.32 ± 0.031	0.35 ± 0.026	+ 9.38*
Lungs	0.42 ± 0.063	0.56 ± 0.097	+ 33.33**
Testicles	1.09 ± 0.117	0.80 ± 0.336	- 26.61*

* P < 0.05; ** P < 0.01; *** P < 0.001

 

Table 2: Selected parameters of blood analysis

Parameter	Control	Test group	t (Student-Fischer) test
Haematocrit [%]	41.5 ± 1.84	53.6 ± 1.55	12.175***
Haemoglobine [g/100 mL]	14.1 ± 0.68	18.4 ± 0.49	14.872***
Urea [mg/100 mL]	28.4 ± 6.41	34.3 ± 6.04	-2.154*
GPT [U/L]	46 ± 11.4	32 ± 5.3	- 3.303**

* P < 0.05; ** P < 0.01; *** P < 0.001