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Description of key information

Assessment of the toxicokinetic behaviour of the substance is limited to the extent that can be derived from the relevant available information.

Key value for chemical safety assessment

Additional information

Absorption

Hf is poorly soluble in water or saline solutions: thus, it is not absorbed efficiently by ingestion. A study realized with radiohafnium found an oral absorption ranging between 0.04 and 0.13 % of the ingested dose in Chinese hamsters (Taylor et al., 1985 - Klimisch 2).

It can be absorbed by inhalation only under its aerosol form (Taylor et al., 1985 –Klimisch2).

Distribution

The metabolism of radiohafnium (175Hf +181Hf) was studied in male rats, Chinese hamsters and marmosets, for periods of up to 168 days (Tayloret al., 1983 -1985).

In rats, radiohafnium (40 KBq) was administered intravenously via a lateral tail vein. After 7 days, the organ distribution was skeleton > skin > muscle > liver > kidneys > testes > spleen > lungs.

In hamsters, radiohafnium was administered subcutaneously by injection of 0.2 cm3of the solution (40 kBq) under the skin of the back. The radiohafnium organ distribution was skeleton greater than skin greaterthan liver greater than muscle , at about 7 days post injection.

Four marmosets, 2 females (aged 4 and 8 years) and 2 males (aged 6 and 9 years), exposed to radiohafnium, were also studied. They were injected intramuscularly into the right thigh with 3 kBq. For males and females, sacrificed respectively after 13 and 97 days, the following percentages of doses found in different organs were: in liver,8.3-12.1 % of the dose injected, bones around 1 % measured in the femur; in the kidneys, 1.5-4.3 %; and in a lesser extent in spleen and lung (Taylor et al., 1985 – Klimisch 2).

Similarly, Riedel et al. (1979) found that, after an intravascular administration of hafnium dioxide colloid in female Wistar rats, hafnium was mainly measured in the liver (between 50 and 89 % of the colloid) and in a lesser extent in spleen (between 3.1 and 7 % of the colloid) and lung (< 1 %).

Metabolism

Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster (Taylor et al., 1983 –Klimisch2).

No dissolution of the metal was detected in soft tissues after hafnium wires were implanted in the subcutaneous tissue of the abdominal region for 2 or 4 weeks (Matsunoet al., 2001).

Fifty-two 8 week old F344/Crl male rats were used to study the metabolism of hafnium tritide. A 30 ml saline suspension of 2 mg of tritide powder (count median diameter 1.04 µm, SD 2.41 µm) was used for the intratracheal instillation. The rats were anesthetized before instillation. Four rats were then assigned for excreta collections and were transferred into individual metabolism cages. Urine and feces were collected daily for 14 days, then for 3 consecutive days at 1, 2, 4 and 6 months. Four rats form each group were sacrificed at 1h, 1-2-3-7-14 days and at 1-2-4-6 months to collect lungs, bronchial lymph nodes, liver kidney; muscle, blood and gastro-intestinal tract. Six months after, 70 % of the dose initially present in the lungs remained in the organ, sign of a very low dissolution rate (Zhou and Cheng, 2003 – Klimisch 2) .

Excretion

Hafnium excretion, following oral administration, is mainly fecal (Venugopal and Luckey, 1978 – Klimisch 4, no more details mentioned and only listed in a book: Metal toxicity in mammals 2).

Following intratracheal instillation of hafnium tritide, after 6 months, 30 % of the dose injected was excreted mainly via feces (98 %) and via urine (2 %) (Zhou and Cheng, 2003 Klimisch 2).

Dissolution in artificial media

To investigate the dissolution potential of Hafnium powder, two studies have been performed in vitro, with the mean of artificial media: sweat medium and gastric fluid.

After 4h agitation at 37°C and sieving with 0.22 µm filter, 1% of dissolved hafnium is quantified by ICP-MS in the sweat medium, which showed the poor dissolution potential in a sweat-like medium with a pH of 6 -7.

After 24h agitation at 37°C and sieving through a 0.22 µm filter, about 25% dissolved hafnium is retrieved by ICP-MS method in the gastric fluid. This last result showed a medium potential to dissolution, but it was concluded that the artificial gastric fluid used (pH 1.5) was not realistic enough to explain what could be the hafnium behavior in human body. Indeed, it is known that hafnium will do whatever it can to stay in the higher Hf(IV) oxidation state, including forming unusual complexes (Chirik PJ, 2007), and it does not allow it to easily dissolved or to go through biological membranes (see Taylor et al., 1985 study with <1% oral absorption results). The artificial gastric fluid used in this study was only composed of glycine, water and hydrochloric acid that could not permit the Hf complexations that occurred in body fluids.