Aluminum antimony nickel silicon titanium vanadium oxide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 250 mg/kg bw/day

Additional information

No data for reproductive 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 reproductive toxicity for the target substance.

There were no specific studies of reproductive toxicity available for Zeolite, cuboidal, crystalline, synthetic, non-fibrous. However, data are available from a repeated oral dose study with special attention to the urogenital system (key study) and a repeated inhalation study with basic observation of reproductive organs (supporting study).

 

The potential toxic effect on the urogenital system was examined in a study in three groups of 40 male COX-SD rats each fed a diet with 0%, 0.125% or 2% (corresponding to approximately 0, 75 and 1250 mg/kg bw/day, respectively) of Zeolite, cuboidal, crystalline, synthetic, non-fibrous (UDL 1078) for 160 or 200 days (Sturm, 1976, RL2).Gross necropsy at 160-days and 200-days sacrifice revealed no remarkable effects on the testes of the control group, and of the groups treated with 0.125% and 2%, respectively.Unremarkable findings (one animal with right testis approximately 1/3 of the expected normal size was observed at the 160 d sacrifice in the 0.125% treatment group; one animal with a small seminal vesicle at 200 d sacrifice in the 2 %-group) were not substance induced and showed no dose-relationship. Therefore, a NOAEL of up to and including 2% Zeolite (UDL 1078) in the diet corresponding to approximately 1250 mg/kg bw/day was determined for testicular effects.

No indication of toxicity to reproductive organs was observed in an additional study with cynomolgus monkeys (Macaca fascicularis).Groups of 3 females and 3 males each were exposed to 0, 1, 6 or 50 mg/m³ Zeolite, cuboidal, crystalline, synthetic, non-fibrous (UDL 1362) dust for 6 hours per day, 5 days a week for a period of 6, 12 or 24 months (Kohrman, 1979, RL2). Findings such as cysts in ovaries, prostates with nodules, minimal reduced spermatogenesis, acute metritis, testes/ovary larger than the other, testes and ovary containing mineralized concretions, slight pigmentation in the ovary were findings recorded in control and/or treatment groups.Histomorphological changes seen in the reproductive organs were not compound-induced and revealed no dose-relationship.Therefore, a NOAEC of 50 mg/m³ for reproductive organs was determined.

Thus, Zeolite, cuboidal, crystalline, synthetic, non-fibrous was considered to have no effects on fertility.

Though the respirability of Aluminium silicate and titanium oxide matrix doted with vanadium, nickel, and antimony is considered negligible, inhalation data from the source substance Zeolite, cuboidal, crystalline, synthetic, non-fibrous are taken into account for assessment of developmental toxicity. For the assessment of the developmental toxicity, the systemic availability of the test material has to be ensured, the route of exposure is irrelevant. As the particle size distribution indicates in general a respirability/bioavailablilty for Zeolite, cuboidal, synthetic, non-fibrous by the inhalation route, the test material is considered to be systemically available and thus the study is considered suitable for assessment of developmental toxicity.

Short description of key information:
fertility (rat): NOAEL = 1250 mg/kg bw/d (RA Zeolite cuboidal)

Effects on developmental toxicity

Description of key information

developmental toxicity (rat, rabbit): NOAEL = 1600 mg/kg bw/d (RA Zeolite cuboidal)

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 600 mg/kg bw/day

Additional information

No data for developmental 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 developmental toxicity for the target substance.

 

Pregnant Sprague Dawley rats were treated daily with Zeolite, cuboidal, crystalline, synthetic, non-fibrous (Type A) with 0, 74, or 1600 mg/kg bw/day on gestation days 6 – 15 per gavage (20 animals per dose) (Nolen and Dierckman, 1978, rat, RL2). Although not performed according to GLP, the key studies were generally performed according to OECD 414. The dams were sacrificed on gestation day 20.Conception rates were high and no maternal, embryo or foetal toxicity was noted. No significant differences were observed in the incidence of soft tissue malformations or of skeletal defects in the treated animals relative to the controls. These data indicate that the test compound was not developmentally toxic in rats at the dose levels tested. The NOAEL was 1600 mg/kg bw/day for maternal toxicity and for developmental toxicity.

Similarly pregnant New Zealand rabbits were treated daily with Zeolite, cuboidal, crystalline, synthetic, non-fibrous (Type A) with 0, 74, 345 or 1600 mg/kg bw/day on gestation days 6 – 18 per gavage (20 animals per dose) (Nolen and Dierckman, 1978, rabbit, RL2). The dams were sacrificed on gestation day 29. No significant differences were observed in the incidence of soft tissue malformations or of skeletal defects in the treated animals relative to the controls. In addition, no maternal toxicity or mortality was observed that could be attributed to the test compound. These data indicate that the test compound was not a developmental toxicant in rabbits at the dose levels tested.The NOAEL was 1600 mg/kg bw/day for maternal toxicity and developmental toxicity.

Thus, Zeolite, cuboidal, crystalline, synthetic, non-fibrous was considered to have no developmental toxicity potential.

 

Additional data for developmental toxicity are available for the following source substance which serves as potential data sources for the analogue approach of Aluminium silicate and titanium oxide matrix doted with vanadium, nickel, and antimony:

- Source chemical 6 - Kaolin:

NOAEL oral (developmental toxiciy) = 10000 mg/kg bw/d; Patterson and Staszak 1977

In accordance with the target substance, the available data for the source substance also provides negative results for developmental toxicity.

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.

 

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 to reproduction/developmental toxicity/teratogenicity according to DSD (67/548/EEC) or CLP (1272/2008/EC).