Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP compliant guideline study, klimisch 1
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In addition to the combined oral repeated dose toxicity study with the reproduction / developmental toxicity screening test performed with cesium potassium fluoroaluminate, additional information from the structural analogue trisodium hexafluoroaluminate has been used to assess the reproductive toxicity of cesium potassium fluoroaluminate.

A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of Nocolok Cs Flux (SM) in rats by oral gavage was conducted according to the OECD guidelines 422 and 407 under GLP conditions. The test item, formulated in water, was administered daily at dose levels of 10, 30 and 100 mg/kg by oral gavage to SPF-bred Wistar Han rats. One control group and three treated groups were tested, each consisting of 10 males and 10 females. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females with offspring were exposed for 50-54 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during 13-15 days of lactation. Females which failed to deliver healthy offspring were exposed for 42 days.

The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), functional observations and locomotor activity (end of treatment), body weight and food consumption (at least at weekly intervals), estrous cycle determination (14 days prior to treatment, 14 days of treatment and during mating until evidence of mating, and on the day of necropsy), clinical pathology (end of treatment), measurement of thyroid hormone T4 (F0-males at the end of treatment and PND 13-15 pups), macroscopy at termination, organ weights and histopathology on a selection of tissues. In addition, the following reproduction/developmental parameters were determined: mating, fertility and conception indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights, anogenital distance, areola/nipple retention and macroscopy). Formulations were analyzed once during the study to assess accuracy and homogeneity and stability.

Accuracy, homogeneity and stability of formulations were demonstrated by analyses. Parental results: There were no treatment-related changes the in-life results, haematology parameters or organ weights. Clinical biochemistry parameters showed treatment-related decreases in total protein and albumin, dose-dependently, in males at 10 mg/kg and above, a decrease in urea in males at 100 mg/kg, and an increase in total cholesterol in both sexes at 100 mg/kg. The changes at 100 mg/kg were considered to be toxicologically relevant. Microscopic examination revealed local treatment-related changes in the glandular stomach suggestive of irritating properties of the test item. These changes consisted of an increased incidence and severity of lymphogranulocytic inflammation in both sexes starting at 10 mg/kg, accompanied by edema in some males at 100 mg/kg and some females at 30 and 100 mg/kg. Additionally, males at 100 mg/kg showed congestion/haemorrhage which correlated with the macroscopically observed dark red/reddish foci in the glandular stomach of these males. Treatment-related vacuolation of the zona glomerulosa in the adrenal gland, slightly above background, was noted at 100 mg/kg in females. In the absence of any degenerative changes, this finding was considered to be non-adverse. No reproduction or developmental toxicity was observed up to the highest dose level tested and therefore 100 mg/kg is considered a NOAEL for reproduction.

For the structural analogue of cesium potassium fluoroaluminate, trisodium hexafluoroaluminate (cryolite), a two-generation toxicity study is available. In this two-generation reproduction study performed according to GLP and EPA Guideline 83 -4, Sprague-Dawley rats (30 per group) were administered trisodium hexafluoroaluminate in the diet at dose levels of 0, 200, 600, or 1800 ppm (corresponding to mean dose levels of 0, 15, 45, and 138 mg/kg/day for males and females). Compound-related systemic toxicity was observed in a dose related manner among both sexes and generations at all dose levels as evidenced by clinical signs of dental fluorosis. Whitening of the upper and/or lower incisors was observed in most treated animals of both generations. Bevelled anterior edge of the lower incisor was observed in 67% of animals from both generations at 1800 ppm. Mottled appearance of the lower incisor was noted at dose levels ≥ 600 ppm in 6%-40% of F1 animals; however, this effect was not dose related.

Reproductive toxicity was observed at 1800 ppm as evidenced by significantly decreased pup body weights during lactation days 7, 14, and 21 (82%-88% of control in F1 offspring) and days 4, 7, 14, and 21 (74%-89% of control in F2 offspring). Gross findings were also observed in pups of both generations at 1800 ppm by the time of weaning. They were manifested as pale kidneys, pale livers and enlarged hearts and were considered to be compound related. No effects were observed on parental reproductive performance.

From this study a NOAEL for fertility of >1800 ppm corresponding to >138 mg cryolite/kg bw/day can be derived. Besides dental fluorosis and teeth whitening, no other compound-related systemic toxic effects could be revealed from this study with daily dosages of up to and including 138 mg cryolite/kg bw/day. Based on the observed decreased mean body weights during lactation for both the F1 and F2 litters and an increased incidence of F1 and F2 animals with pale/white liversand/or kidneys and enlarged hearts at weaning at 1800 ppm, a NOAEL for developmental toxicity of 600 ppm / 45mg cryolite/kgbw/day is derived from this study.

There is no indication for fertility risks caused by cesium potasium fluoroaluminate based on the results of the combined oral repeated dose toxicity study with reproduction/developmental toxicity screening with cesium potassium fluoroaluminate and the two-generation study with the structural analogue trisodium hexafluoroaluminate. Therefore, a quantitative assessment is not considered necessary for this endpoint.

Effects on developmental toxicity

Description of key information
 A NOAEL of 30 mg/kg bw for systemic maternal effects and a NOAEL of 100 mg/kg bw for developmental toxicity was established in a combined oral repeated dose toxicity study with reproduction/developmental toxicity screening test with Cesium potassium fluoroaluminate (OECD 422, GLP). Additional information from the structural analogue trisodium hexafluoroaluminate (cryolite) has been used to assess the developmental toxicity of cesium potassium fluoroaluminate. The cesium moiety of the molecule was assessed by using the results of a developmental toxicity study with cesium hydroxide. Based on these results cesium potassium fluoroaluminate is not to be considered as developmental toxicant.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP compliant guideline study, klimisch 1
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In addition to the combined oral repeated dose toxicity study with the reproduction/developmental toxicity screening test performed with cesium potassium fluoroaluminate, additional information from the structural analogue trisodium hexafluoroaluminate (cryolite) has been used to assess the developmental toxicity of cesium potassium fluoroaluminate. The cesium moiety of the molecule was assessed by using the results of a developmental toxicity study with cesium hydroxide.

A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of Nocolok Cs Flux (SM) in rats by oral gavage was conducted according to the OECD guidelines 422 and 407 under GLP conditions. The test item, formulated in water, was administered daily at dose levels of 10, 30 and 100 mg/kg by oral gavage to SPF-bred Wistar Han rats. One control group and three treated groups were tested, each consisting of 10 males and 10 females.Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females with offspring were exposed for 50-54 days, i.e. during 2 weeks prior to mating, during mating, during postcoitum, and during 13-15 days of lactation. Females which failed to deliver healthy offspring were exposed for 42 days.

The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), functional observations and locomotor activity (end of treatment), body weight and food consumption (at during mating until evidence of mating, and on the day of necropsy), clinical pathology (end of treatment), measurement of thyroid hormone T4 (F0-males at the end of treatment and PND 13-15 pups), macroscopy at termination, organ weights and histopathology on a selection of tissues. In addition, the following reproduction/developmental parameters were determined: mating, fertility and conception indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights, anogenital distance, areola/nipple retention and macroscopy). Formulations were analyzed once during the study to assess accuracy and homogeneity and stability. Accuracy, homogeneity and stability of formulations were demonstrated by analyses. Parental results: There were no treatment-related changes the in-life results, haematology parameters or organ weights. Clinical biochemistry parameters showed treatment-related decreases in total protein and albumin, dosedependently, in males at 10 mg/kg and above, a decrease in urea in males at 100 mg/kg, and an increase in total cholesterol in both sexes at 100 mg/kg. The changes at 100 mg/kg were considered to be toxicologically relevant. Microscopic examination revealed local treatment-related changes in the glandular stomach suggestive of irritating properties of the test item. These changes consisted of an increased incidence and severity of lymphogranulocytic inflammation in both sexes starting at 10 mg/kg, accompanied by edema in some males at 100 mg/kg and some females at 30 and 100 mg/kg. Additionally, males at 100 mg/ kg showed congestion/haemorrhage which correlated with the macroscopically observed dark red/reddish foci in the glandular stomach of these males. Treatment-related vacuolation of the zona glomerulosa in the adrenal gland, slightly above background, was noted at 100 mg/kg in females. In the absence of any degenerative changes, this finding was considered to be non-adverse. No reproduction or developmental toxicity was observed up to the highest dose level tested and therefore 100 mg/kg is considered a NOAEL for development.

Trisodium hexafluoroaluminate (cryolite) was investigated for prenatal developmental toxicity in mice in a GLP compliant study according to EPA Guideline 83 -3. Cryolite was administered by oral gavage to female CD-1 mice (25/group) at dose levels of 0, 30, 100 or 300 mg/kg bw/day once daily from gestation days 6 to 15 (WIL Research Laboratories, 1991). There was increased mortality at 300 mg/kg bw/day. The glandular portion of the stomach was red beginning at 100 mg/kg bw/day. In addition, females in the 300 mg/kg bw/day group exhibited dark red contents of the stomach.Fetuses at 300 mg/kg bw/day exhibited bent ribs and bent limb bones.The study reveals severe maternal toxicity in terms of mortality and signs of toxicity in the gastrointestinal tract induced at dosages of>100 mg cryolite/kg bw/day leading to derivation of a NOAEL for maternal toxicity of 30 mg cryolite/kg bw/day. Based on the observation of skeletal anomalies at the dose level of 300 mg cryolite/kg bw/day also a NOAEL for developmental toxicity of 100 mg cryolite/kg bw/day can be derived from the study. As these anomalies were only reported at dose levels showing severe maternal toxicity, the effects are not considered to be indicative for a substance specific teratogenic potential of cryolite.

Developmental toxicity of cesium hydroxide was evaluated in a prenatal developmental study in Wistar rats according to OECD Guideline 414 (Toxi-coop, 2012). The oral treatment of pregnant rats from gestation days 5 to 19 (i.e. the day before Caesarean section) with cesium hydroxide monohydrate did not cause death, clinical signs or macroscopical alterations at necropsy at the dose levels of 10, 40 and 150 mg/kg bw/day. Cesium hydroxide monohydrate did not reveal any adverse effect on the pregnancy of the dams, the preimplantation loss, the intrauterine mortality of the conceptuses, the number of viable fetuses and their sex distribution. The development of fetuses evaluated at external, visceral and skeletal examination and determined by the fetal body weight was undisturbed, the test item caused no fetal malformations at the dose levels of 10, 40 and 150 mg/kg bw/day.

Justification for classification or non-classification

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for effects on fertility and development.

During the two-generation study (in rats) with the structural analogue trisodium hexafluoroaluminate, the critical adverse effects that had been revealed were impairment of postnatal growth evidenced by significantly decreased pup body weights during lactation as well as gross pathological changes in several organs (kidney, liver, heart) of the pups (not statistically significantly increased) observed at dose levels of 138 mg/kg bw/day without any significant maternal toxicity. No effects were observed that could indicate that pups under lactation were already affected in utero (normal weight at birth and absence of visual defects). From the data that are available it could be concluded that the observed effects in the pups were due to the lactation itself. The effects may have been caused by reduced amount of milk available to the pups or the altered nutritional composition of the milk or by the presence of fluoride in the milk. Therefore, cryolite is proposed to be classified with R64 in accordance to Directive 67/548/EEC and H362 (May cause harm to breast-fed children) under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008).

The same classification should be applied for cesium potassium fluoroaluminate.

Additional information