Cobalt molybdate

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

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: Basic data given.

Data source

Reference

Reference Type:

publication

Title:

Effects of Chronic Exposure to Cobalt Chloride on the Fertility and testes in Mice

Author:

Elbetieha, A. et al.

Year:

2007

Bibliographic source:

Journal of Applied Biological Sciences 2(1): 01-06

Materials and methods

Principles of method if other than guideline:

The effect of 12-week ingestion of cobalt chloride on the fertility of male mice is investigated in a drinking water study with 3 different concentrations. After the exposure period, the male mice are mated with untreated females.

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

cobalt chloride hexahydrate

IUPAC Name:

cobalt chloride hexahydrate

Constituent 2

Reference substance name:

7791-13-1

EC Number:

616-574-6

Cas Number:

7791-13-1

IUPAC Name:

7791-13-1

Details on test material:

- Name of test material (as cited in study report): cobalt chloride hexahydrate
- Analytical purity: no data

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Faculty of Medicine, Jordan University of Science and Technology
- Age at study initiation: 60 days
- Weight at study initiation: approx. 32 g
- Diet: standard receipes (manufactured by the Faculty of Veterinary Medicine at Jordan University of Science and Technology, Irbid, Jordan); ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

12 weeks

Frequency of treatment:

daily via drinking water

Duration of test:

males: 12 weeks treatment, 10 days post-treatment (mating period)
females: no treatment, mated females were killed 20 days after mating

Doses / concentrations

Remarks:

Doses / Concentrations:
200, 400 and 800 ppm (corresponding to 25.66 ± 2.34, 46.91 ± 4.78 and 93.01 ± 6.76 mg/kg bw/day, respectively)
Basis:
nominal conc.

No. of animals per sex per dose:

10 males per dose
(after exposure every male was caged with 2 untreated females for mating)

Control animals:

other: plain water

Details on study design:

Cobalt-exposed and control males were sacrificed after 12 weeks of cobalt chloride ingestion and the 10 day period of mating.
Examinations:
- Organ weights/evaluation: paired testes, seminal vesicles (stripped of seminal fluid), epididymides and preputial glands
- Testicular and epididymal sperm counts
- Histological evaluation of testes

Females were sacrificed, 10 days after end of the mating period.
Examinations: number of pregnant females, number of implantation sites/females, number of viable fetuses/females, number of resorptions, and number of females with resorptions

Statistics:

Differences between control and test groups were analyzed using either Student's t-test or Fisher's exact test using StatMost 2.5 Windows software/DataMost Corporation. A p-value less than 0.05 were considered significant.

Results and discussion

Effect levels

1

Dose descriptor:

LOAEL

Remarks:

fertility

Effect level:

25.7 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: decreased sperm counts (decreased implantations, increased number of resorptions, decreased number of viable fetuses)

2

Dose descriptor:

LOAEL

Remarks:

fertility

Effect level:

6.4 mg/kg bw/day (actual dose received)

Based on:

element

Remarks:

Co

Sex:

male/female

Basis for effect level:

other: decreased sperm counts (decreased implantations, increased number of resorptions, decreased number of viable fetuses)

3

Dose descriptor:

LOAEL

Remarks:

fertility

Effect level:

23.8 mg/kg bw/day (actual dose received)

Based on:

other: CoMoO4

Sex:

male/female

Basis for effect level:

other: decreased sperm counts (decreased implantations, increased number of resorptions, decreased number of viable fetuses)

Observed effects

General effects
- Mortality: 2/10 and 1/10 animals died in the 800 and 400 ppm group, respectively (during the 10th week)
- Clinical signs of toxicity: none
- Body weight gain: reduced compared to control group in all treated animals
- Average daily fluid intake: reduced compared to control group in all test groups

Effects on fertility
- No. pregnant females: reduced in females mated with males of the 400 (66.7%) and 800 (43.8%) ppm groups (control group: 95%)
- No. of implantations: reduced in females mated with males of the 200 (5.67 ± 2.02) and 400 (5.42 ± 1.68) ppm groups (control group: 7.89 ± 2.38)
- No. of viable fetuses: reduced in females mated with males of all treatment groups (5.00 ± 2.14, 4.67 ± 1.83 and 5.83 ± 1.94 in the 200, 400 and 800 ppm group, respectively; control group: 7.74 ± 2.4)
- Total no. of resorptions and no. of animals with resorptions: increased in females mated with exposed males of all treatment groups (no. resorptions/no. implantation sites: 3/150, 9/81, 9/65 and 10/45 in the control, 200, 400 and 800 ppm group, respectively; % animals with resorptions: 16%, 67%, 63% and 70% in the control, 200, 400 and 800 ppm group, respectively)

Effects on reproductive organs
- Organ weights: decreased absolute epididymal weights at 800 ppm, significantly decreased testes weights in all dose groups, significant increase in absolute weight of seminal vesicles at 400 and 800 ppm, increased relative weights of preputial glands at 400 ppm
- Testicular and epididymal sperm counts: decreased epididymal sperm counts in all dose groups (86.7%, 86.2% and 78.1% of the control value with increasing dose); decreased testicular sperm counts at 400 and 800 ppm (77.4% and 74.1% of the control value, respectively), decreased daily sperm production at 400 and 800 ppm (64.2% and 57.4% of the control value, respectively)
- Histology of testis: necrosis of both the seminiferous tubules and the interstitial tissue, congested blood vessels, hypertrophy of the interstitial Leydig cells and degeneration of the spermatogonial cells in all sections of testes collected from mice of the 400 and 800 ppm groups

Any other information on results incl. tables

Table 1: Details on results: reproductiv organs

Treatment (ppm)	No. of males	Epididymis weight (mg)	Testes weight (g)	Seminal vesicles weight (g)	Preputial gland weight (g)
Control (water)	10	32.31 ± 1.66	0.21± 0.01 (57.75 ± 3.89)	0.13± 0.02 (36.36 ± 6.82)	0.096 ± 0.01 (26.07 ± 2.51)
200	10	31.88 ± 1.46	0.19± 0.01** (55.45 ± 3.18)	0.13± 0.03 (35.57 ± 7.46)	0.107 ± 0.015 (30.44 ± 4.86)*
400	9	31.75 ± 1.45	0.18± 0.01*** (53.08 ± 3.33)*	0.20± 0.02** (61.91 ± 8.24)***	0.096 ± 0.016 (29.32 ± 5.90)
800	8	29.80 ± 0.93***	0.15± 0.02**** (46.28 ± 7.31)***	0.23± 0.07*** (68.32 ± 21.94)***	0.094 ± 0.023 (28.81 ± 7.13)

Results are expressed as mean ± SD

Results in brackets: relative organ weights, expressed as mg/10g bw

* p < 0.5, **p < 0.01, *** p < 0.005, **** p < 0.0001 (student’s t-test)

 

Applicant's summary and conclusion

Conclusions:

Long-term exposure of adult male mice to cobalt chloride hexahydrate adversely affected various fertility parameters.