Vanadyl pyrophosphate

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented peer reviewed study

Data source

Reference

Reference Type:

publication

Title:

Reproductive toxicity evaluation of vanadium in male mice

Author:

Llobet JM, Colomina MT, Sirvent JJ, Domingo JL & Corbella J

Year:

1993

Bibliographic source:

Toxicology. 80(2-3): 199-206, 1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Investigation of the effects of vanadium on male fertility

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Sodium metavanadate

EC Number:

237-272-7

EC Name:

Sodium metavanadate

Cas Number:

13718-26-8

IUPAC Name:

Sodium metavanadate

Details on test material:

- Name of test material (as cited in study report): Sodium metavanadate
- Molecular formula (if other than submission substance): O3-V.Na
- Molecular weight (if other than submission substance): 121.9
- Smiles notation (if other than submission substance): [V](=O)(=O)[O-].[Na+]
- InChl (if other than submission substance): 1/Na.3O.V/q+1;;;-1;/rNa.O3V/c;1-4(2)3/q+1;-1
- Structural formula attached as image file (if other than submission substance): see Fig. 1

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Panlab (Barcelona, Spain)
- Age at study initiation: No data
- Weight (on supply): 28-30 g
- Fasting period before study: No
- Housing: No data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23 deg C
- Humidity (%): 40 - 60 %
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Concentration in vehicle: 0, 0.10, 0.20, 0.30 and 0.40 mg/mL

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

In the drinking water for 64 days with concentration adjusted twice weekly on the basis of bodyweight and water consumption

Frequency of treatment:

Continuous

Duration of test:

64 days exposure, 4 days mating, 10 days gestation (78 days total)

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 40, 80 and 80 mg/kg body weight/day
Basis:
nominal in water

No. of animals per sex per dose:

24 males/group

Control animals:

yes

Details on study design:

Male mice were exposed in the drinking water for 64 days. Groups were subdivided and 8 animals/group were mated with untreated females and 16 animals/group used for pathology and sperm analysis. Mating/cohabitation was for 4 days with 2 untreated females. Females were killed 10 days following the end of the mating period (i.e. Day 10-14 of gestation).
Groups of males were

Statistics:

Bartlett's test for homogeneity. If homogeneous ANOVA, if non-homogeneous Kruskal-Wallis. Differences relative to controls examined using either Student's t-test or modified t-test

Results and discussion

Observed effects

Reduced weight gain and significantly lower terminal bodyweight noted at 80 mg/kg/day.
Reduced epididymal weight noted at 80 mg/kg/day.
Reduced sperm counts noted at 60 and 80 mg/kg/day.
Reduced fertility noted at 60 and 80 mg/kg/day

Any other information on results incl. tables

No signs of toxicity were observed in any of the treated groups.

Reduced weight gain noted at 80 mg/kg/day, resulting in significantly lower mean terminal bodyweights.

Mean absolute and relative testes weights were comparable in all groups. Mean absolute epididymal weights were significantly lower at 80 mg/kg/day, although relative weight was unaffected by treatment.

The reproductive performance of treated males was significantly reduced at 60 and 80 mg/kg/day, although no dose-response relationship was apparent.

Testicular and/or epididymal sperm counts were significantly reduced at 60 and 80 mg/kg/day. Sperm motility was slightly (but not significantly) reduced at 80 mg/kg/day and the proportion of morphologically abnormal spermatozoa was slightly increased in this group.

No gross or microscopic lesions were observed in the testes and epididymides and epididymal tubular diameter was unaffected by treatment.

Fertility and litter parameters

	Dose level (mg/kg/day)
	0	20	40	60	80
No. pregnant females	13/16	12/16	12/16	7/16	10/16
Pregnant females (%)	81.3%	75.0%	75.0%	43.8%**	62.5%**
No. Implantations	13.7	13.1	15.3	15.5	13.2
No. Early resorptions	0.9	0.8	1.3	0.8	1.6
No. Late resorptions	0.0	0.5	0.0	0.3	0.0
No. Dead foetuses	0.0	0.1	0.2	0.0	0.0
No. Live foetuses	12.8	11.7	13.8	14.4	11.6

**significantly different to controls (p<0.001)

Organ weights / sperm analysis

	Dose level (mg/kg/day)
	0	20	40	60	80
Terminal bodyweight (g)	41.4	42.0	39.4	41.0	36.2*
Left testis (mg)	126.9	127.3	136.2	162.5	121.3
Right testis (mg)	135.1	128.2	136.7	133.4	129.2
Total testes weight (mg)	262.1	256.1	273.0	266.0	251.0
Total testes weight (%)	0.64	0.61	0.69	0.65	0.70
Left epididymis (mg)	47.1	49.6	49.1	46.6	41.7*
Right epididymis (mg)	48.3	51.2	49.4	48.7	42.6*
Total epididymis weight (mg)	95.5	100.8	98.6	95.4	84.4**
Total epididymis weight (%)	0.23	0.24	0.25	0.23	0.24
Spermatid count (x10^6/g testis)	91.8	126.3**	96.2	84.5	64.7**
Spermatid count (x10^6/testis)	12.3	15.9**	12.6	11.3	8.4*
Spermatid count (x10^6/testis/ g body weight)	0.30	0.38*	0.32	0.28	0.20*
Spermatozoa count (x10^6/g epididymis)	687	682	714	388*	471*
Spermatozoa count (x10^6/epididymis)	33.1	34.7	35.1	18.6*	19.9**
Spermatozoa count (x10^6/epididymis/ g body weight)	0.80	0.83	0.88	0.45*	0.55*
% motile	28	34	31	28.6	17.6
% abnormal	8	5	7	6	12
Tubular diameter (µm)	197.4	203.3	187.7	198.2	183.5

*significantly different to controls (p<0.01); **p<0.001

Applicant's summary and conclusion

Conclusions:

The reproductive toxicity of sodium metavanadate has been investigated in male mice by administration in the drinking water at dose levels of 0, 20, 40, 60 or 80 mg/kg/day for 64 days before mating with untreated females. Reproductive performance, organ weights, testicular pathology and sperm parameters were evaluated.
Reduced weight gain was seen in males at the highest dose level. A significantly reduced pregnancy rate was seen at 60 and 80 mg/kg/day with no dose-response relationship apparent. Reduced epididymis weight was observed at 80 mg/kg/day although testis weights were unaffected by treatment. Sperm counts were significantly decreased at 60 and 80 mg/kg/day but sperm motility was not affected. Histopathological examination revealed that the testes and epididymides were normal and contained normal appearing sperm.
These findings suggest that high dose levels of sodium metavanadate may to have an adverse effect on male fertility in mice.

Executive summary:

The reproductive toxicity of sodium metavanadate has been investigated in male mice by administration in the drinking water at dose levels of 0, 20, 40, 60 or 80 mg/kg/day for 64 days before mating with untreated females.  Reproductive performance, organ weights, testicular pathology and sperm parameters were evaluated.  

Reduced weight gain was seen in males at the highest dose level. A significantly reduced pregnancy rate was seen at 60 and 80 mg/kg/day with no dose-response relationship apparent. Reduced epididymis weight was observed at 80 mg/kg/day although testis weights were unaffected by treatment. Sperm counts were significantly decreased at 60 and 80 mg/kg/day but sperm motility was not affected. Histopathological examination revealed that the testes and epididymides were normal and contained normal appearing sperm.

These findings suggest that high dose levels of sodium metavanadate may to have an adverse effect on male fertility in mice.