Tricobalt dicitrate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study which meets basic scientific principles (limited documentation of the results).

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Materials and methods

Principles of method if other than guideline:

Conducted similar to OECD 413, male and female mice were exposed to cobalt(II)sulfate heptahydrate aerosol for 6 hours per day, 5 days per week, and 13 weeks. Sperm morphology and vaginal cytology evalutions were also performed.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

10026-24-1

EC Number:

600-050-9

Cas Number:

10026-24-1

IUPAC Name:

10026-24-1

Constituent 2

Reference substance name:

cobalt(II)sulfate heptahydrate

IUPAC Name:

cobalt(II)sulfate heptahydrate

Details on test material:

- Name of test material (as cited in study report): cobalt(II)sulfate heptahydrate
- Molecular formula (if other than submission substance): CoSO4*7H2O
- Molecular weight (if other than submission substance): 281 g/mol
- Analytical purity: 99%
- Other: The pH of aqueous solutions of cobalt sulfate heptahydrate was measured at three concentrations. Solutions of 0.01, 0.1, and 1 M were found to have pH values of 6.3, 6.2 and 5.2, respectively.

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms, Inc. (Germantown, NY, USA)
- Age at study initiation: 7 weeks
- Housing: individual housing
- Diet (e.g. ad libitum): NIH 07 rat and mouse ration (Zeigler Bros., Inc., Gardners, PA); ad libitium except during exposure periods

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7 - 25.2
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Hazleton 2000, Lab Products, Inc.
- System of generating particulates/aerosols: Cobalt(II)sulfate heptahydrate aerosol was generated from an aqueous solution by nebulisation using dried compressed air. The aerosol was diluted to the desired concentration with air from the chamber air-conditioning system.
- Method of particle size determination: Cascade impactor samples were taken to determine aerosol size distribution. The mass median aerodynamic diameter of the aerosol for all exposures ranged from 0.83 to 1.10 µm. Cobalt sulfate hydration in the aerosol distribution line was determined by ultraviolet/visible spectroscopy. Hydration ratios of 7.66 and 7.67 were determined for two samples taken during the studies.

TEST ATMOSPHERE
- Brief description of analytical method used: Three real-time aerosol monitors (Model RAM-1, GCA Environmental Instruments) were used to determine the concentration of the aerosol in the exposure chambers once every 20 minutes throughout the exposure period.

Details on mating procedure:

no mating procedure

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Three real-time aerosol monitors (Model RAM-1, GCA Environmental Instruments) were used to determine the concentration of the aerosol in the exposure chambers once every 20 minutes throughout the exposure period.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours per day, 5 days per week

Details on study schedule:

no mating procedure

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
3, 10, 30 mg/m3
Basis:
other: nominal conc.; calculated as the anhydrous salt of cobalt(II)sulfate heptahydrate

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2.93±0.275; 9.95±0.579; 30.0±1.64 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Animals distributed to weight classes and then assigned to cages and groups by a table of random numbers.

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice per day

BODY WEIGHT: Yes
- Time schedule for examinations: weighed initially and once per week thereafter

Oestrous cyclicity (parental animals):

estrous cycle, vaginal cytology

Sperm parameters (parental animals):

Parameters examined in male animals:
testis weight, sperm motility, sperm morphology

Litter observations:

No mating procedure and therefore no litter.

Postmortem examinations (parental animals):

SACRIFICE
- At study termination, all surviving animals were sacrificed with carbon dioxide and necropsied. Histopathological examinations and determination of organ weights were performed.

Postmortem examinations (offspring):

No mating procedure and therefore no litter.

Statistics:

The analysis of organ weight and male reproductive system data was carried out by using the non-parametric multiple comparison procedures of Dunn (1964) or Shirley (1977) to assess the significance of pairwise comparisons between dosed and chamber control groups. Jonckheere´s test (Jonckheere, 1954) was used to evaluate the significance of dose-response trends and to determine whether Dunn´s or Shirley´s test was more appropriate for pairwise comparisons.
The proportion of time spent in each stage of the estrous cycle was compared by using the Wilks criterion statistic (Wilks, 1932) of the multivariate analysis of variance procedure, which was performed after an arc sine transformation of the data.

Offspring viability indices:

No mating procedure and therefore no litter.

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

CLINICAL SIGNS AND MORTALITY
Two of ten males exposed to 30 mg/m3 died before termination of the study. No observed clinical signs appeared to be related to the exposure, with exception of rapid breathing and skin discoloration in the two male mice that died during week 11.

BODY WEIGHT
Mean body weights of mice exposed to 30 mg/m3 and females exposed to 10 mg/m3 were lower than those of controls throughout the study. The final mean body weight of mice at 30 mg/m3 was 14% lower than that of the controls for males and 22% lower for females.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE
The estrous cycle was significantly longer in female mice exposed to 30 mg/m3.

REPRODUCTIVE FUNCTION: SPERM MEASURES
The number of abnormal sperm in mice exposed to 30 mg/m3 was significantly increased, and sperm motility was significantly reduced in mice exposed to 3, 10, or 30 mg/m3.
At the highest concentration, atrophy of the testis was observed, which consisted of a loss germinal epithelium in the seminiferous tubules; more severly affected testes also contained foci of mineralisation.

ORGAN WEIGHTS
The absolute testis weight and the testis weight to body weight ratio were significantly decreased for males exposed to 30 mg/m3. The epididymal weight was significantly lower than that of controls for mice exposed to 30 mg/m3.

OTHER
No consistent or dose-related hematologic effects were observed.

Effect levels (P0)

1

Dose descriptor:

LOAEC

Effect level:

0.3

Sex:

male/female

Basis for effect level:

other: calculated as the anhydrous salt of cobalt(II)sulfate heptahydrate significant decrease in sperm motility

2

Dose descriptor:

LOAEC

Effect level:

0.5 mg/m³ air

Sex:

male/female

Basis for effect level:

other: CoC6H6O7; recalculated value significant decrease in sperm motility

Results: F1 generation

Details on results (F1)

No mating procedure and therefore no litter.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No NOAEC for toxicity to reproduction was identified.