Calcium tin trioxide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

40 mg/kg bw/day

Additional information

From existing studies of toxicokinetic behaviour of Tin (IV) dioxide and Tin (II) chloride, it can be concluded that the toxicokinetic profiles of the two substances appear to be similar. Minor differences between Tin (II) and Tin (IV) in their absorption and distribution indicate that Tin (II) may be a bit more toxic than Tin (IV). Therefore Tin (II) chloride can be used as a structural surrogate for Tin (IV) dioxide in the reproductive toxicity study.

In a multigeneration study, CPB:WU rats were given tin in the diet at 0, 200, 400, or 800 mg/kg (as Tin (II) chloride) for three generations. From the test, Tin did not affect growth of the parents, fertility, numbers of offspring per litter, or birth weight (WHO, 2005). Therefore the NOAEL of Tin (IV) dioxide was considered to be 800 mg/kg in diet for rat (NOEC_{mammal, food_repro.}). According to REACH guidance “Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for environment” the NOAEL_{mammal, food_chr}= NOEC_{mammal, food_chr}/ CONV_mammal(CONVmammal for Rattus norvegicus (> 6 weeks) was default as 20). The NOAEL_repro of Tin (IV) dioxide to rat, 40 mg/kg bw per day can be estimated by above method.

Short description of key information:
Tin did not affect growth of the parents, fertility, numbers of offspring per litter, or birth weight at level of 800 mg/kg (as Tin II) in diet.

Effects on developmental toxicity

Description of key information

Groups of 9–10 female Sprague-Dawley rats were given diets containing tin at 0, 125, 156, 250, 312, 500, or 625 mg/kg (as tin salts (SnF2, NaSn2F5, NaSn2Cl5) throughout pregnancy (to day 20).  At these doses, the stannous (Tin II) has no teratogenic effect to rats. 

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

31.3 mg/kg bw/day

Additional information

Various animal data on inorganic compounds indicate even lower toxicity of Tin (IV) than Tin (II) and insoluble inorganic tin than soluble inorganic tin. Both Tin (II) oxide and Tin (IV) dioxide didn’t induce any effect in rats in repeated dose toxicity studies. Based on above, the use of Tin (II) oxide, Tin (IV) chloride, Tin (II) fluoride and Tin (II) chloride, as well as other stannic or stannous compounds as a structural surrogate for Tin (IV) dioxide (CAS No. 18282-26-4) for pre natal toxicity study is feasible.

When groups of 9–10 female Sprague-Dawley rats were given diets containing tin at 0, 125, 156, 250, 312, 500, or 625 mg/kg (as tin salts (SnF2, NaSn2F5, NaSn2Cl5)) throughout pregnancy (to day 20). Untreated rats had foetuses containing 0.64 mg Sn/kg. Foetal tin values were found to be elevated (0.8-1.3 mg Sn/kg) when the maternal diets contained tin salts. The greatest number of foetal resorptions was found in groups fed sodium pentafluorostannite, but the observation was not considered toxicologically significant. There were no effects on the numbers of litters, resorptions, or live foetuses per litter. Mean placental and foetal weights were also unaffected (Theuer et al., 1971). Therefore the NOAEL of Tin (IV) dioxide was considered to be 625 mg/kg in diet for rat (NOEC_{mammal, food_develop.}). According to REACH guidance “Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for environment” the NOAEL_{mammal, food_chr}= NOEC_{mammal, food_chr}/ CONV_mammal(CONVmammal for Rattus norvegicus (> 6 weeks) was default as 20). The NOAEL_develop of Tin (IV) dioxide to rat, 31.3 mg/kg bw per day can be estimated by above method.

In a multigeneration study, CPB:WU rats were given tin in the diet at 0, 200, 400, or 800 mg/kg (as Tin(II) chloride)

for three generations. Within this multigeneration study, a teratogenicity study was carried out using 20 F2b females per dose level. On visceral and skeletal examination, there was no increase in the incidence of foetal malformations (WHO, 2005). Based on above information, it can be concluded that the stannous (Tin II) has no teratogenic effect to rats. Based on existing information, the tin (IV) is lower toxic than Tin (II). Therefore the substance tin dioxide has no developmental or teratogenic concern to animals or human.

Justification for classification or non-classification

Based on existing information, the substance is not need to be classified under Regulation (EC) No 1272/2008 for any category of Reproductive/developmental toxicity. For the same reason it does not satisfy with the classification criteria of Directive 67/548/EEC.