Aluminium fluoride

Endpoint summary

Description of key information

In a 12-month dietary feeding study conducted with the read-across substance Cryolite (trisodium hexafluoroaluminate), LOAEL values of 95 and 105 mg/kg body weight/day (the low-dose) were derived for male and female dogs, respectively (Tompkins, 1992).  No other oral studies were identified.
The key 28-day inhalation study was a GLP rat study conducted according to OECD testing guideline 412, in which a NOAEC of 7 mg/m3 (the mid-dose) was identified (Muijser and Junker, 2006).  The key subchronic study was a 5-month study in rats that tested aluminum fluoride at a concentration equivalent to 0.41 mg aluminum/m3; however, limited details on experimental methods and results were presented (ATSDR, 2008).
Dermal exposure is not considered the most relevant route of exposure; no dermal studies were identified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

95 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

7 mg/m³

Additional information

Information regarding the speciation of both the registered substance, aluminium fluoride (AlF3), and a read-across substance, cryolite, was sourced from a literature article reporting computer-aided QSAR estimates of the speciation of the substances in aqueous media utilizing SOLGASWATER (version Win SGW) model. The author tabulated the expected Al(III) speciation at pH 7.2 and an ionic strength of 0.15, intended to represent a physiological medium, for additions of AlF3 and of cryolite of 0.001 mM, 0.1 mM and 10 mM. At 0.001 mM, both substances gave identical distributions of only hydroxy-Al species, at 0.1 mM both substances gave very similar distributions of predominantly hydroxy- and hydrox-fluoro-Al species, and at 10 mM both substances gave very similar distributions of predominantly hydroxy-fluoro- and fluoro-Al species. On the basis that exposure to the registered substance, AlF3, or to the read-across substance, cryolite, is expected to generate very similar proportions of essentially the same aluminium complexes within the solubility range of AlF3, cryolite is considered to be an appropriate surrogate for AlF3.

A single oral study was identified (Tompkins, 1992); this study was similar in design to OECD testing guideline 452. The read-across substance Cryolite was administered in the diet to Beagle dogs for a period of 12 months. Dietary levels were 0, 3000, 10000, or 30000 ppm, equivalent to 0, 95, 366, or 1137 mg/kg body weight/day for males and 0, 105, 387, or 1139 mg/kg body weight/day for females. Four (4) animals per sex were included in each group. Endpoints assessed included clinical signs, body weight and body weight gain, haematology, clinical chemistry, and microscopic examinations. The LOAEL was reported to be 3000 ppm (equivalent to 95 and 105 mg/kg body weight/day in males and females, respectively), based on increases in emesis, nucleated cells in males, renal lesions, and a decrease in urine specific gravity in females.

The key 28-day inhalation study was that of Muijser and Junker (2006). This GLP study was conducted according to OECD testing guideline 412. Male and female Wistar rats (5/sex/dose) were exposed by nose-only inhalation to aluminum trifluoride at concentrations of 0, 1, 7, or 50 mg/m³. Exposures were conducted for 6 hours/day, 5 days/week for 4 weeks. A full examination was conducted with the exception of detailed clinical observations, ophthalmoscopy, and urinalysis. A NOAEC of 7 mg/m³was reported, based on observations in the high-dose group that included increased absolute and relative lung weights (males and females), increased absolute and relative liver weights (males), changes in tracheobronchial lymph nodes, and other lung inflammatory changes.

The key subchronic inhalation study was a 5-month study in rats that was summarized by a secondary source (ATSDR, 2008). In this study, Sprague-Dawley rats were exposed to aluminum fluoride for 6 hours/day, 5 days/week for 5 months. The concentration of aluminum fluoride was reported to result in exposure to 0.41 mg aluminum/m³; no other information on the exposure conditions was reported. Lungs were observed for alveolar damage and body and brain weights were examined (further details not provided). Suggestive evidence of alveolar macrophage damage was observed following the 5-month exposure; increases in lysozyme levels were observed in the lavage fluid.  No body weight effects were observed. No brain weight effects were observed although tissues were not examined histologically.

 

Justification for classification or non-classification

The available in vivo repeated dose studies on both the notifiable substance and an acceptable surrogate did not identify any toxicologically significant changes in the test animals. Thus, the data are conclusive but not sufficient for classification.