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:

supporting study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published literature study: read across from similar compound

Data source

Reference

Reference Type:

publication

Title:

Spermicidal Activity of Metallocene Complexes Containing Vanadium(IV) in Humans

Author:

D'Cruz OJ, Ghosh P & Uckun FM

Year:

1998

Bibliographic source:

Biology of Reproduction 58, 1515-1526

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Computer-assisted sperm analysis was used to evaluate the spermicidal activity of 8 metallocene dihalides, 5 vanadocene di-pseudohalides and 3 disubstituted derivatives.

GLP compliance:

no

Remarks:

: published literature study

Type of method:

in vitro

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

8 metallocene dihalides(vanadocene dichloride [VDC], titanocene dichloride [TDC], zirconocene dichloride [ZDC], molybdocene dichloride [MDC], hafnocene dichloride [HDC], vanadocene dibromide [VDB], bis[methylcyclopentadienyl] vanadium dichloride [VMDC] and vanadocene diiodide [VDI]); 5 vanadocene di-pseudohalides (vanadocene diazide [VDA], vanadocene dicyanide [VDCN], vanadocene dioxycyanate [VDOCN], vanadocene dithiocyanate [VDSCN] and vanadocene diselenocyanate [VDSeCN]); and 3 disubstituted derivatives (vanadocene ditriflate [VDT], vanadocene monochloro oxycyanate [VDCO] and vanadocene monochloroacetonitrilo tetrachloro ferrate [VDFe]).

Test animals

Species:

other: not applibale, in vitro study

Details on test animals or test system and environmental conditions:

Semen was provided by 12 healthy volunteers who had been repeatedly found to have normospermic semen according to World Health Organization criteria for normal donor specimen. Semen samples were allowed to liquefy for 30 min at 37C, after which an aliquot was removed for analysis.

Administration / exposure

Route of administration:

other: in vitro

Vehicle:

other: sperm were exposed to the test material in appropriate culture media

Details on exposure:

Motile fractions of sperm were isolated prior to a sperm immobilisation assay with exposure to the test compound for 3 hours. In experiments investigating sperm acrosome reactions, exposure time was 3 hours.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

3 hour incubation of sperm with the test material

Frequency of treatment:

Single exposure

Duration of test:

3 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
1.9-250 uM
Basis:
nominal conc.
: serial dilutions of all test substances

No. of animals per sex per dose:

Not applicable

Details on study design:

No further details.

Statistics:

Results for the various numerical sperm function parameters were presented as mean + SD values. Comparisons between VDC-treated sperm relative to sperm motility parameters and acrosomal loss were performed using a paired, two-tailed Student's t-test. A p value of < 0.05 was considered
significant. Nonlinear regression analysis was used to find the EC50 values.

Results and discussion

Observed effects

Metallocene complexes containing titanium, zirconium, molybdenum and hafnodium were inactive, however all 12 of the vanadocene complexes investigatd elicited potent spermicidal activity at nanomolar to micromolar concentrations. The order of efficacy was VDSeCN > VDSCN > VDB > VMDC > VDCN > VDA > VDC > VDOCN > VDI > VDT > VDFe > VDCO. No disruption of the acrosomal membrane was noted , as determined by high-resolution low-voltage scanning electron microscopy. The sperm-immobilizing activity of the vanadocene complexes was rapid and irreversible, since the
treated sperm underwent apoptosis as determined by the flow cytometric annexin V binding assay, DNA nick end-labeling and confocal laser scanning microscopy.

Any other information on results incl. tables

No further details.

Applicant's summary and conclusion

Conclusions:

Potent spermicidal activity in vitro was demonstrated for metallocene compounds containing vanadium, whereas this activity was not seen for complexes of other metals investigated. The authors conclude that metallocene complexes containing vanadium (IV), especially vanadocene diselenocyanate may be useful as contraceptive agents.

Executive summary:

Computer-assisted sperm analysis was used to evaluate the spermicidal activity of eight metallocene dihalides (vanadocene dichloride [VDC], titanocene dichloride [TDC], zirconocene dichloride [ZDC], molybdocene dichloride [MDC], hafnocene dichloride [HDC], vanadocene dibromide [VDB], bis[methylcyclopentadienyl] vanadium dichloride [VMDC] and vanadocene diiodide [VDI]); five vanadocene di-pseudohalides (vanadocene diazide [VDA], vanadocene dicyanide [VDCN], vanadocene dioxycyanate [VDOCN], vanadocene dithiocyanate [VDSCN] and vanadocene diselenocyanate [VDSeCN]); and three disubstituted derivatives (vanadocene ditriflate [VDT], vanadocene monochlorooxycyanate [VDCO] and vanadocene monochloro acetonitrilo tetrachloroferrate [VDFe]). The metallocene complexes containing titanium, zirconium, molybdenum, and hafnodium were inactive, however all 12 vanadocene complexes elicited potent spermicidal activity at nanomolar or micromolar concentrations with an order of efficacy VDSeCN > VDSCN > VDB > VMDC > VDCN > VDA > VDC > VDOCN > VDI > VDT > VDFe > VDCO. This activity was achieved without disruption of the acrosomal membrane, as determined by high-resolution low-voltage scanning electron microscopy. The sperm-immobilising activity of the vanadocene complexes was rapid and irreversible, since the treated sperm underwent apoptosis as determined by the flow cytometric annexin V binding assay, DNA nick end-labeling, and confocal laser scanning microscopy. The authors conclude that metallocene complexes containing vanadium (IV), especially VDSeCN, may be useful as contraceptive agents.