Iodine pentafluoride

Endpoint summary

Description of key information

The lowest LOAEL of 0.55 mg/kg bw/day was observed in the 2-year study with rats with potassium iodide in the drinking water.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

0.55 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data published in a peer-reviewed journal

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

0.72 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

Proprietary study conducted according to GLP, and comparable to current guidelines.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Due to the fact that the substance violently reacts with moisture and produces hydrofluoric and iodic acids, classification for toxicity is based on fluoride and iodide:

The repeated dose toxicity of fluoride was performed in 2 oral and 3 inhalation studies. In a 6 -month oral (drinking water) rat study, the effects of exposure to NaF were limited to reduced weight gain, dental fluorosis, thickening and ulceration of the gastric mucosa at the highest dose level of 300 ppm; gastric effects were also seen at 100 ppm. The fluoride content of plasma, bone and teeth increased with dose levels (NTP 1990). The NOEL for this study was 30 ppm, however these local effects are considered not to be relevant for the risk assessment. Therefore 100 ppm of NaF in the drinking water (5.2 and 6.4 mg/kg bw for male and female rats, respectively) was considered a NOAEL in this 6 -month rat study. In a 6 -month oral mouse study, mortality attributable to acute nephrosis was seen at the highest dose level of 600 ppm (NTP 1990). Skeletal effects were seen in males at 50 ppm and in both sexes at the higher dose levels. Therefore the LOAEL was determined to be 50 ppm (5.1 mg/kg bw). In a published study (Sadilova 1974), female rats were exposed to 1 mg/m3 HF 6 hours/day for 1 month. Effects were noted on the teeth, bones and respiratory tract. Two proprietary studies (Placke 1990, 1991) give over-all NOAEL for repeated inhalatory exposure in male and female rats of 0.72 mg/m3 (actual HF concentration) for a 6 hours per 5 days per week for 91 days exposure regimen (1991) and a NOAEL of 0.88 mg/m3 (actual HF concentration) for a 6 hours per 5 days per week for 2 weeks (1990). No adverse effects were noted at these concentrations. At higher concentrations death, tissue irritation, dental malformations, slight changes in haematological and clinical chemistry parameters, and changes in several organ weights were observed.

The repeated dose toxicity of iodide was examined In a chronic toxicity study (Takegawa 2000) in which male and female F344/DuCrj rats received potassium iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 2 years. The average daily intakes (males - females) were 0, 0.55 - 0.66, 5.31 - 6.73. and 53.03 - 66.59 mg/kg bw/day. Survival rates of male rats were decreased in the100 and 1000 ppm groups. Body weights in the 1000 ppm groups of both sexes were decreased in the latter half of the treatment period. The incidence of thyroid follicular dilatation was increased in the 10, 100 and 1000 ppm groups of both sexes (the incidence of this non-neoplastic lesion did not decrease with decreasing dose levels). In the submandibular salivary gland of male adn female rats of the 1000 ppm group squamous cell carcinomas were observed, along with focal acinar atrophy and/or ductular proliferation, frequently accompanied by squamous metaplasia. No KI-related induction of any lesions was apparent in any other organ or tissue. The lowest dose level of 0.55 mg/kg bw/day was considered to be a LOAEL based on the non-neoplastic thyroid change.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Lowest LOAEL was observed in this study.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Lowest NOAEL was observed in this study.

Justification for classification or non-classification

Due to the fact that the substance violently reacts with moisture and produces hydrofluoric and iodic acids, classification for toxicity is based on fluoride and iodide. Based on the available studies, the substance needs to be classified as STOT Rep. Exp. Cat. 1; H372 (Causes damage to organs through prolonged or repeated exposure) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. According to the EU Directive 67/548/EEC the substance needs to be classified as T; R48/23/25 (Toxic: danger of serious damage to health by prolonged exposure through inhalation and if swallowed).