Aluminum antimony nickel silicon titanium vanadium oxide

Endpoint summary

Description of key information

NOAEL (rat, subchronic, oral) = 250 mg/kg bw/d (RA Zeolite cuboidal)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

No data for repeated dose toxicity are available for the target substance Aluminium silicate and titanium oxide matrix doted with vanadium, nickel, and antimony.Therefore, data from the analogue approach source substance Zeolite cuboidal were applied to cover the endpoint repeated dose toxicity for the target substance:

 

Zeolite, cuboidal, crystalline, synthetic, non-fibrous (Sasil) was administered for 90 consecutive days to rats in concentrations of 0, 1000 ppm, 5000 ppm, and 10000 ppm (w/w) in the diet, corresponding to approximately 50-60, 250-300, and 500-600 mg/kg bw/day for males and females, respectively (Bartnik, 1976, RL2). No mortality was observed. Behaviour, feed consumption, body weight gain, haematology and blood chemistry were not significantly different from control. Results of the urinalysis of the 1000 and 5000 ppm test group were comparable to the control. The only differences between the test and control groups were found in the 10000 ppm test substance group. In this group the effects regarding the function and histopathology of kidneys and bladder were found (i.e., diminished urine secretion, hematuria and ketone bodies in the urine, 12/20 male animals revealed urinary calculi mainly composed of Si). The histological examination showed a hyperplastic reaction of the transitional bladder epithelium in rats with calculi. The determined elemental concentration of Fe, Zn, and Al of the 10000 ppm group was not significantly different from control. However, the silicon content of the kidneys was considerably higher when compared to controls, especially in the male group fed with the highest dose level. The cobalt content of the liver decreased significantly in the treated female rats when statistically analyzed with the t-test. The copper content in the livers of the female rats treated with 10000 ppm Zeolite (Sasil) was comparable to the control; the copper values for the treated male rats had increased significantly when compared to the control.

The NOAEL was determined to be 5000 ppm, which can be estimated to equal approximately 250 mg/kg bw/day for males and 300 mg/kg bw/day for females, respectively.

Additional data for repeated dose toxicity after inhalation are available for the following source substances which serve as potential data sources for the analogue approach of Aluminium silicate and titanium oxide matrix doted with vanadium, nickel, and antimony:

- Source chemical 5 - Aluminium oxide (Gross 1973)

- Source chemical 6 - Kaolin (Altekruse et al. 1984; Sepulveda et al 1983; Kennedy et al. 1983; Olge et al 1989; Rundle et al. 1993)

No adverse effects were observed in these studies that would justify a classification of the source substance for repeated dose toxicity. However, as the inhalation route is considered not relevant for the target substance due to the low exposure potential to the alveolar region of the lung, the available repeated dose inhalation data from the source substances are not considered relevant.

The respective references for the source substance data can be found in the data matrix of the justification for the analogue approach, which can be found either in the CSR or as attachment in Iuclid section 13.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys; urogenital: urinary bladder

Justification for classification or non-classification

Based on the results obtained, Aluminium silicate and titanium oxide matrix doted with vanadium, nickel, and antimony does not fulfill the criteria to be classified for toxicity after repeated administration according to DSD (67/548/EEC) or CLP (1272/2008/EC).