Iodine pentafluoride

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

Metabolism

Iodine pentafluoride is a highly reactive and corrosive substance which undergoes an immediate decomposition in contact with water or moisture according to the following reaction scheme: IF5 + 3 H2O → HIO3+ 5HF

Thus, one mole of iodic acid and five moles of hydrofluoric acid are formed as a result of the reaction of one mole IF5 with water. Both iodic acid and hydrofluoric acid are relatively strong acids and will undergo dissociation into their respective protons and anions in aqueous media, forming iodate and fluoride.

Available toxicokinetic data on iodate indicate that upon uptake in the body at least at low concentrations it is quantitatively reduced to iodide by a non-enzymatic reaction (Bürgi, 2001). Leblond and Süe (1941) reported that within 40 minutes after rats were exposed intravenously to radioactive iodate containing 0.75 mg radioactive iodine, all iodate was converted into iodide. Olsen et al. (1979) reported a half-life of 14 minutes when rabbits received an intravenous injection of 30 mg/kg bw radiolabelled sodium iodate. These results are similar to those reported by Taurog et al. (1966), who reported that following the intravenous administration of 0.75 µmol of radioiodate (95 µg iodine) to rats or 8 µmol of radioiodate (1 mg iodine) to rabbits, within 3 minutes radioiodate could no longer be detected in the blood, and all the administered radioactive iodine was in the form of iodide. Webster et al. (1966) administered a higher single dose of 200 mg/kg bw potassium iodate to three mongrel dogs; during the first 24 hours both iodate and iodide were present in the urine. During the next 24-48 hours the iodide diminished and the iodate disappeared. Within 4 days only traces of iodide were present in the urine. Ingestion of 60 mg/kg bw potassium iodate, resulted in the appearance of iodate in the urine only for a brief time within a few hours after ingestion, and the amount relative to the quantity of iodide was small. These observations indicate that much of the iodate is reduced to iodide in the body.

Taurog et al. (1966) demonstrated that the reduction of iodate in the body is a non-enzymatic process and depends on the availability of sulfhydryl groups, e.g. in glutathione. The reaction between iodate and glutathione proceeds as follows: 6 GSH + IO3^-→ 3 G-S-S-G + I^-+ 3 H2O. Available data indicate that other –SH groups in e.g. haemoglobin and in other proteins may also be oxidised by iodate. Overall, the available data provide convincing evidence that at least at low doses iodate is quantitatively reduced by non-enzymatic reactions and becomes available to the body as iodide. Therefore, exposure of tissues to iodate, with the exception of perhaps the gastrointestinal mucosa, might be limited. At high doses, however, the bodily capacity of iodate-reducing –SH-containing proteins might be exhausted, which leads to a part of iodate being excreted unmetabolised, as observed by Webster et al. (1966) in dogs. However, the dose of 200 mg/kg bw at which the excretion of both iodate and iodide was observed, was severely toxic to dogs, with one out of three animals dying within a week. At a lower dose of 60 mg/kg bw, at which already most of the iodate was converted into iodide within a few hours, also clinical signs of toxicity, including vomiting, were noted.

Absorption

Initially, DNEL derivation was based on the LOAEL determined in a two-year oral rat study with potassium iodide, using the REACH default absorption values for extrapolation from the oral route to the inhalation and dermal routes. For final DNEL derivation the human Tolerable Daily Intake for iodine established by WHO was used. In this derivation human absorption data were used to perform route-to-route extrapolation. An oral and inhalation absorption of 100% was assumed since inorganic compounds of iodine are readily and extensively absorbed by both the inhalation and oral routes (WHO, 2009). For dermal absorption, a ratio oral to dermal absorption of 10:1 was used since dermal absorption in humans has been experimentally shown to be 1% or less of the applied dose (WHO, 2009), but as IF5 is a corrosive substance, the integrity of the skin could be compromised and therefore a dermal absorption of 10% was assumed.

-WHO (2009). Concise International Chemical Assessment Document 72. Iodine and inorganic iodides: Human health aspects. Geneva, World Health Organization.