Cryolite, tripotassium

Endpoint summary

Description of key information

Based on read-across from multiconstituent aluminium potassium fluoride, the  most critical effects of potassium cryolite after repeated inhalation exposure are expected to be effects on the lungs. Based on the available study, the overall NOAEC for local effects is 1.21 mg/m3. The overall systemic NOAEC is >3.08 mg/m3.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

3.08 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP compliant guideline study, klimisch 1

System:

respiratory system: lower respiratory tract

Organ:

lungs

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

1.21 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP compliant guideline study, klimisch 1

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

No repeated dose toxicity study is available for potassium cryolite and therefore the results of a sub-chronic toxicity study with the structural analogue multiconstituent aluminium potassium fluoride are used instead (for details see Read-across justification as attached in section 13).

Inhalation

The inhalation toxicity of aerosols of multiconstituent aluminium potassium fluoride was studied in a subchronic (90-day) study in rats (performed according to OECD guideline 413 and under GLP). Groups of 10 male and 10 female rats were exposed to test substance concentrations of 0 (control), 0.32, 1.21, or 3.08 mg/m3.

Increases in both absolute and relative numbers of neutrophils were observed in females of the high concentration group at the end of the exposure period, but a statistical significant degree was reached in absolute number only. At the end of the recovery period, absolute and relative neutrophil counts were still higher in females. The increase in the percentage of neutrophils in these females was accompanied by a decrease in the percentage of lymphocytes at that time. Absolute and relative lung weights were higher in females of the high concentration at the end of the exposure period; a statistical significant degree was observed in absolute weight only. In males no such changes were seen. At the end of the recovery period, no changes in lung weights were observed.  Macroscopic examination at necropsy did not reveal treatment-related changes. Microscopic examination of the respiratory tract at the end of the 90-day exposure period revealed a concentration-related change in the lungs consisting of typical alveolar macrophage accumulations in animals of the mid and high concentration group. A tissue reaction appeared absent. The macrophage accumulations persisted after a recovery period of 60 days. The macrophages were somewhat smaller in size when compared to those in animals of the high concentration group at the end of the exposure period, but more conspicuous because their cytoplasm was darkly stained. Despite the persistent presence of the macrophages, a tissue reaction was still absent. The presence of the macrophages are considered a physiological response to the exposure and therefore not considered adverse as such. Therefore, 1.21 mg/m3 is considered a NOAEC for local effects.The overall systemic NOAEC is 3.08 mg/m3. These values will be taken forward to risk assessment of potassium cryolite.

Justification for classification or non-classification

In a sub-chronic inhalation study with the read-across candidate multiconsituent aluminium potassium fluoride a NOAEC of 1.21 mg/m3 was established based on local effects in the lungs. Therefore the substance potassium cryolite needs to be classified as STOT Rep. Exp. Cat. 1; H372 for the inhalation route according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.