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Toxicological information

Carcinogenicity

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Description of key information

A study was reported by Oppenheimer et al. (1956), in which two pieces of metal foil were sterilised and then imbedded in 25 rats, one on either side of the abdominal wall. The rats were observed until the incisions were completely healed and were subsequently examined at weekly intervals for signs of tumour formation. 844 days after the tantalum was imbedded in the rats two malignant tumours had been recorded and only two rats survived. Due to methodological deficiencies, the low number of animals and the missing control group, this study was disregarded.

This publication was citied in a review article by Kerwien (1996), in which tantalum was reported to be an experimental tumorigenic or tumour causing substance. However, overall systemic industrial poisoning is apparently unknown. Tantalum and its compounds are not listed as either presumptive or possible human carcinogens in the U.S. federal registry of suspected human carcinogens. The review article by Kerwien (1996) contained limited detail, not enough needed to make an assessment on the reliability of the findings presented. It also referred to secondary data and was therefore assigned a reliability score of 4.

The substance and its structural analogues were found to be non-mutagenic from the conclusions of the genetic toxicity tests, and no adverse effects are predicted from repeated dose studies with subcutaneously implanted tantalum as inert control for uranium or the structural analogue TaCl5. Furthermore, a review article by Miller (1998) assessed the risk for carcinogenesis and mutagenesis from depleted uranium embedded fragments, whereby animals with tantalum embedded fragments served as a control showing no carcinogenic effects. These findings are in line with the available human data on tantalum exposure, reporting no effects despite the long-term use of tantalum in surgical implants for a number of years. Based on this data, testing for this endpoint is not required.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

According to column 2 (specific rules for adaptation from column 1) point 8.9.1, under Annex X of the regulation EC no. 1907/2006, a study may be proposed if:

- the substance has a widespread dispersive use or there is evidence of frequent or long-term human exposure; and

- the substance is classified as mutagen category 3 or there is evidence from the repeated dose study(ies) that the substance is able to induce hyperplasia and/or pre-neoplastic lesions.

A study was reported by Oppenheimer et al. (1956), in which two pieces of metal foil were sterilised and then imbedded in 25 rats, one on either side of the abdominal wall. The rats were observed until the incisions were completely healed and were subsequently examined at weekly intervals for signs of tumour formation. 844 days after the tantalum was imbedded in the rats 2 malignant tumours had been recorded and only 2 rats survived. The latent period was determined to be 714 days. The tumours were determined to be fibrosarcomas. The possible mechanism for tumour formation was tentatively predicted to be related to the physical form of the tantalum imbedded (i.e. as a foil) since, in an analogous study with plastic, it was found that more tumours were obtained with plain plastics than with perforated film or fibres (textiles) or powders. The physical state was therefore predicted to be an important factor. Due to methodological deficiencies, the low number of animals and the missing control group, this study was disregarded. Furthermore it is the only study reporting tumorigenic evidence of tantalum exposition.

This publication was citied in a review article by Kerwien (1996), in which tantalum was reported to be an experimental tumorigenic or tumour causing substance. However, overall systemic industrial poisoning is apparently unknown. Tantalum and its compounds are not listed as either presumptive or possible human carcinogens in the U.S. federal registry of suspected human carcinogens. However, under unusual circumstances following implantation of tantalum in animal tissue, it has caused cancer. Apparently, the smoothness of the implanted tantalum sheet plays a role, with highly polished surfaces potentially leading to cancer in animals. Thus, sometimes tantalum is listed as being a non-specific, surface carcinogen. However, this effect has not been observed in humans despite its long-term use in medical implants. The review article by Kerwien (1996) contained limited detail, not enough needed to make an assessment on the reliability of the findings presented. It also referred to secondary data and was therefore assigned a reliability score of 4.

The substance and its structural analogues were found to be non-mutagenic from the conclusions of the genetic toxicity tests, and no adverse effects are predicted from repeated dose studies with subcutaneously implanted tantalum as inert control for uranium or the structural analogue TaCl5. Furthermore, a review article by Miller (1998) assessed the risk for carcinogenesis and mutagenesis from depleted uranium embedded fragments, whereby animals with tantalum embedded fragments served as a control showing no carcinogenic effects. These findings are in line with the available human data on tantalum exposure, reporting no effects despite the long-term use of tantalum in surgical implants for a number of years. Based on this data, testing for this endpoint is not required.

Justification for classification or non-classification

In accordance with criteria for classification as defined in Annex I, Regulation 1272/2008, the target substance tantalum does not require classification for carcinogenicity based on the fact that despite its use as a medical implant for a number of years no carcinogenic effects have been observed.