Calcium tin trioxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.7 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.7 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Additional information - workers

For acute DNEL-systemic effects, based on "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", generally systemic effects after acute oral and dermal exposure should in a first tier be assessed using the corresponding long-term DNELs. A DNEL for acute toxicity is only established for the effects of peak exposures as these peaks can be significantly higher than the average daily exposure and the long-term DNEL (to be complied with on average over e.g. a working day) may be insufficient to limit them. To tin dioxide, no such peak exposure existed, so long term DNELs is sufficient and also directly used as acute DNELs-systemic effects.

For DNEL -local effects, the substance was not as an irritant to eye and skin, so the DNEL is unnecessary to be generated for local effects.

For long-term DNEL – systemic effects (dermal) from the toxicokinetics assessment for tin dioxide a maximum of 5 % dermal absorption rate has been considered based on guidance. For derivation of the long-term systemic dermal DNEL, on one hand the oral NOAEL = 40 mg/kg bw/d (Sn²⁺) was converted into a corrected dermal NOAEL of 800 mg/kg bw/d (5 % dermal absorption rate for tin dioxide, and all absorbed tin was assumed to be converted to Sn²⁺) according to the procedure, recommended in the current guidance document (R8, ECHA 2010). The following assessment factors (AF) were applied: •allometric scaling = 4 (R8, ECHA 2010) •remaining differences = 2.5 (R8, ECHA 2010) •intraspecies = 5 (for work R8, ECHA 2010) •exposure duration = 1 (since the NOAEL was derived from a multi-generation test) •quality of whole database = 1 (based on validity of studies performed).  Total AF = 4 x 2.5 x 5 x 1 x 1 = 50. => Consequently, the dermal long-term systemic DNEL derived for workers was 800 / 50 = 16 mg/kg bw/day.

 

On the other hand, the occupational exposure limit for tin inorganic tin was published by German Committee on Hazardous Substances (Ausschuss für Gefahrstoffe – AGS) as Arbeitsplatzgrenzwerte – AGW. The value published is 2 mg/m³which can be taken as start point to calculate the DNEL. 8 hours inhalation volume is 10 m³for worker with body weight of 70 kg (R8, ECHA 2010).5 % dermal absorption rate was assumed for tin dioxide. The converted reference value for dermal exposure was calculated as 2 x 10/5%/70 = 5.7 mg/kg bw.Since the start point is an occupational exposure limit, the AF can be assumed as 1. Therefore the long-term systemic DNEL (dermal) derived for workers was5.7 mg/kg bw by this method. Pragmatically the lower one was chosen as the long-term systemic DNEL (dermal) derived for workers in risk assessment, 5.7 mg/kg bw.

 

For long-term DNEL – systemic effects (Inhalation), there are no data on inhalation toxicity. However the occupational exposure limit for tin inorganic tin was published by German Committee on Hazardous Substances (Ausschuss für Gefahrstoffe – AGS) as Arbeitsplatzgrenzwerte – AGW. The value published is 2 mg/m³.Since the start point is an occupational exposure limit, the AF can be assumed as 1. Therefore the long-term systemic DNEL derived for workers directly was 2 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Additional information - General Population

For acute DNEL-systemic effects, based on "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", generally systemic effects after acute oral and dermal exposure should in a first tier be assessed using the corresponding long-tem DNELs. A DNEL for acute toxicity is only established for the effects of peak exposures as these peaks can be significantly higher than the average daily exposure and the long-term DNEL (to be complied with on average over e.g. a working day) may be insufficient to limit them. To tin dioxide, no such peak exposure existed, so long term DNELs is sufficient and also directly used as acute DNELs-systemic effects.

For DNEL -local effects, the substance was not as an irritant to eye and skin, so the DNEL is unnecessary to be generated for local effects.

 

From the toxicokinetics assessment for tin dioxide a maximum of 5 % dermal and oral absorption rates have been considered based on guidance. For derivation of the long-term systemic dermal and oral DNELs, on one hand the oral NOAEL = 40 mg/kg bw/d (Sn2+) was converted into a corrected dermal/oral NOAEL of 800 mg/kg bw/d (5 % dermal absorption rate for tin dioxide, and all absorbed tin was assumed to be converted to Sn2+) according to the procedure, recommended in the current guidance document (R8, ECHA 2008). The following assessment factors (AF) were applied: •allometric scaling = 4 (R8, ECHA 2010) •remaining differences = 2.5 (R8, ECHA 2010) •intraspecies = 10 (for general population R8, ECHA 2010) •exposure duration = 1 (since the NOAEL was derived from a multi-generation test) •quality of whole database = 1 (based on validity of studies performed).  Total AF = 4 x 2.5 x 10 x 1 x 1 = 100. => Consequently, the oral and dermal long-term systemic DNELs derived for general population was 800 / 100 = 8 mg/kg bw/day. On the other hand, Tin was previously evaluated for tolerable intake for humans by JECFA in 1966, 1970, 1971, 1975, 1978, and 1982. A provisional maximum tolerable daily intake of 2 mg of tin per kg bw was established by the committee. Since the same absorption rate (5%) was assumed to both oral and dermal routs, the provisional maximum tolerable daily intake of 2 mg/kg bw was directly used as a long-term DNEL – systemic effects (oral and dermal). Pragmatically the lower one was chosen as the long-term systemic DNEL derived for general population via both oral and dermal routes in risk assessment, 2 mg/kg bw.

There are no data on inhalation toxicity. Considering a provisional maximum tolerable daily intake of 2 mg of tin per kg bw was established by the committee, this value can be used as a start point to calculate the long-term inhalation route-systemic effects (general population). The body weight is 60 kg for general population. 24 hours respiration volume: 20 m³/person. In addition, since the start point is a TDI, the AF can be assumed to be 1. DNEL (chronic, general population) = 2 x 60/20 = 6 mg/m³.