Vanadyl pyrophosphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

The developmental and behavioural outcomes of exposure to vanadium as vanadyl sulphate (vanadium in its +4 oxidation state), has 
been studied in the rat in a post-natal developmental toxicity study. Pregnant dams were exposed from 3 days before parturition up to weaning. Reduced viability and body growth in the offspring occurred which remained after weaning.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50.5 mg/kg bw/day

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a screening study of reproductive toxicity, sodium metavanadate (vanadium in its +5 oxidation state) showed no adverse effects on fertility. Treatment did not result in maternal toxicity. The NOEL for systemic toxicity was considered to be 20 mg/kg/day (8.36 mg/kg/day vanadium). Assuming vanadium to be the toxicant, this equates to a dose of 50.5 mg/kg/day BTN/A. While no significant adverse effects on fertility, reproduction and parturition in treated rats was observed, development of the offspring was significantly decreased from birth and during lactation. This occurred at all dose levels investigated and theNOEL for reproductive / developmental toxicity could not be determined. The lowest dose level investigated, 5 mg/kg/day (2.09 mg/kg/day vanadium), may be regarded as a LOAEL. Assuming vanadium to be the toxicant, this equates to a dose of 12.6 mg/kg/day BTN/A.

Data are available from studies on other vanadium salts administered either by teh oral route or by intraperitoneal injection. Interpretation of the results from these is difficult when the route of admnistration and potential influence of systemic toxicity is considered.

Short description of key information:
Most reliable study is a one generation screening study on sodium metavanadate (vanadium in its +5 oxidation state) which showed no adverse effects on fertility at 20 mg/kg/day (8.36 mg/kg/day vanadium).

Effects on developmental toxicity

Description of key information

Two studies of prenatal developmental toxicity are available. A mouse study on vanadyl sulphate pentahydrate (vanadium in its +4 oxidation state) resulted in a No Observed Effect Level (NOEL) for maternal toxicity, embryotoxicity, foetotoxicity and teratogenicity less than 37.5 mg/kg/day (7.55 mg/kg/day vanadium). Assuming vanadium to be the toxicant, this equates to a dose of 45.6 mg/kg/day BTN/A. A similar study undertaken in the rat on sodium metavanadate (vanadium in its +5 oxidation state) used methods similar to those described in OECD TG No. 414. The No Observed Adverse Effect Level (NOAEL) for embryo/foetotoxicity was 10 mg/kg/day (4.18 mg vanadium/kg/day). Assuming vanadium to be the toxicant, this equates to a dose of 25.3 mg/kg/day BTN/A. In a screening study of reproductive toxicity, sodium metavanadate (vanadium in its +5 oxidation state) showed no adverse effects on fertility but development of the offspring was significantly decreased from birth and during lactation. This occurred at all dose levels investigated and the lowest dose level investigated, 5 mg/kg/day (2.09 mg/kg/day vanadium), may be regarded as a LOAEL. Assuming vanadium to be the toxicant, this equates to a dose of 12.6 mg/kg/day BTN/A.

Effect on developmental toxicity: via oral route

Dose descriptor:

LOAEL

25.3 mg/kg bw/day

Additional information

A prenatal developmental toxicity study has been undertaken in the mouse on vanadyl sulphate pentahydrate (vanadium in its +4 oxidation state) using methods similar to those described in OECD TG No. 414. Maternal toxicity was apparent as decreased weight gain and reduced body weight in pregnant mice treated with vanadyl sulphate pentahydrate at doses of 37.5, 75 or 150 mg/kg/day. Effects on foetal weights and lengths, in addition to an increased incidence of poorly ossified skeletal elements at all dose levels was seen as embryofoetotoxicity. Treatment resulted in increased incidence of external malformations and gross, visceral and skeletal variations with cleft palate and micrognathia being the major gross malformations seen at the highest dose level (150 mg/kg/day). The No Observed Effect Level (NOEL) for maternal toxicity, embryotoxicity, foetotoxicity and teratogenicity was less than 37.5 mg/kg/day (7.55 mg/kg/day vanadium). Assuming vanadium to be the toxicant, this equates to a dose of 45.6 mg/kg/day BTN/A.

 

A similar study undertaken in the rat on sodium metavanadate (vanadium in its +5 oxidation state) also used methods similar to those described in OECD TG No. 414. There was a relatively high incidence of abnormalities of hemorrhagic character in the treated groups, unusual in type and frequency, and therefore attributed to the treatment. The No Observed Adverse Effect Level (NOAEL) for embryo/foetotoxicity was 10 mg/kg/day (4.18 mg vanadium/kg/day). Assuming vanadium to be the toxicant, this equates to a dose of 25.3 mg/kg/day BTN/A.

 

In a screening study of reproductive toxicity, sodium metavanadate (vanadium in its +5 oxidation state) showed no adverse effects on fertility. Treatment did not result in maternal toxicity. The NOEL for systemic toxicity was considered to be 20 mg/kg/day.

While no significant adverse effects on fertility, reproduction and parturition in treated rats was observed, development of the offspring was significantly decreased from birth and during lactation. This occurred at all dose levels investigated and the NOEL for reproductive / developmental toxicity could not be determined. The lowest dose level investigated, 5 mg/kg/day (2.09 mg/kg/day vanadium), may be regarded as a LOAEL. Assuming vanadium to be the toxicant, this equates to a dose of 12.6 mg/kg/day BTN/A.

The two developmental toxicity studies are regarded as being more robust than the screening study and the lowest NOAEL from these - 4.18 mg vanadium/kg/day which, assuming vanadium to be the toxicant, equates to a dose of 25.3 mg/kg/day BTN/A - has been used.

Toxicity to reproduction: other studies

Additional information

The developmental and behavioural outcomes of exposure to vanadium as vanadyl sulphate (vanadium in its +4 oxidation state), has

been studied in the rat in a post-natal developmental toxicity study.

Pregnant dams were exposed from 3 days before parturition up to weaning (when pups were 25 days old). After weaning, pups continued to receive the same treatment that had been received by their respective dams, up to 100 days of age. Open-field observations and motor activity were assessed at 1 month of age. Food and water intake over a 24 hour period was measured at 2 months of age. A working memory test was performed at 100 days of age, based on the differential exploration of familiar and new objects.

The results indicate that exposure to vanadium during the perinatal period up to weaning significantly reduces viability and body growth in the offspring which remains significant after weaning.

Justification for classification or non-classification

The weight of evidence from available data suggest a concern for effects on fertility. Vanadium, if absorbed, does appear to have an influence on male fertility by direct effects on the testis. Many of the vanadium salts investigated have significant water solubility when compared with vanadyl pyrophosphate (BTN/A) and this is considered to strongly influence bioavailability. It is not possible to predict that vanadium in vanadyl pyrophosphate will be sufficiently labile to give rise to the effects described with other vanadium salts. Precautionary classification in accordance with the criteria stated in EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 appears justified.

 

There is a potential concern for developmental toxicity however, such effects mainly occur in the presence of maternal toxicity and it is judged that the significance/severity of effects are insufficient to require classification in accordance with the criteria stated in EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.