Tin sulphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.67 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

216.85 mg/m³

Explanation for the modification of the dose descriptor starting point:

There is experimental data for sub-chronic repeated dose toxicity by the oral and inhalatory route, of tin chloride or tin monoxide respectively. The long-term DNEL is derived from the repeated oral and repeated inhalation toxicity study. The DNEL considered the most appropriate is then selected.

Repeated dose via oral route as starting point

A NOAEL of 2500 ppm (equivalent to 175.7 mg/kg/day) was determined for the substance tin chloride (CAS no. 7772-99-8) in an oral sub-chronic repeated-dose toxicity study in rats (OECD TG 408, GLP). This value was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/0.38 m³/kg/day, the absorption rates (oral 50 %, inhalation 100 %; in accordance with ECHA Guidance R.8 the absorption rate of the starting route is half that of the end route), the standard respiratory volume in humans/ worker respiratory volume (6.7 m³ (8 h) / 10 m³ (8 h)) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

 

NOAEC corrected = 175.7 mg/kg bw/day * 1/0.38 m³/kg/day * 50/100 * (6.7 m³/10 m³) * 1.4 = 216.85 mg/m³

Repeated dose via inhalation as starting point

A NOAEL of 9.19 µg/L (9.19 mg/m³) was determined in a repeated dose inhalation study on tin monoxide (OECD 412, GLP).

The NOAEL was converted into inhalatory NOAEC for duration of exposure (6h exposure in animal study versus 8h exposure for workers) and for increased respiratory volumes during light activity (6.7 m³ standard respiratory volume for a worker in 8 hours at rest versus 8 m³ standard respiratory volume for a worker at light activity).

The bioavailability between experimental animals and humans at the relevant level of exposure is assumed to be the same; therefore no further correction was necessary.

As such, the corrected NOAEC was derived as follows:

NOAEC corrected= 9.19 mg/m³ * (6h/8h) * (6.7/10) = 4.62 mg/m³

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Default (sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling should be applied in case of oral-to-inhalation extrapolation

AF for other interspecies differences:

2.5

Justification:

default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans

AF for intraspecies differences:

5

Justification:

default for workers

AF for the quality of the whole database:

1

Justification:

The quality of the database is considered to be good. No additional assessment factor due to the use of read-across data is deemed nessecary, as it was fully agreed by ECHA in the decision letter, that data generated with tin sulphate can be used for evaluating the hazard of tin(II) chloride and vice versa.

AF for remaining uncertainties:

1

Justification:

default (no remaining uncertainties are identified)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.241 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

41.8 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

81.024 mg/m³

Explanation for the modification of the dose descriptor starting point:

The substance was classified as inhal. Acute Tox 4 (H332) based on an inhalation acute toxicity study on stannous oxalate (inhalative LC0 = 0.5 mg/L = 500 mg/m³), OECD TG 436, Dreher 2012). Furthermore, there is a 5 -day inhalation preliminary toxicity study with tin monoxide available, which was designed to assess the systemic toxic potential of tin monoxide in a 1 week (6 hours per day, 5 days a week) inhalation study in RccHan™;WIST rats. In the following the repeated dose toxicity study via inhalation according to OECD 412 had been conducted.

The inhalative NOAEL of 41.8 mg/m³ of the preliminary Dose-range finder for the 28 -day study was selected as the dose descriptor starting point for DNEL derivation. It was converted into a corrected inhalatory NOAEC by applying the Haber's Law to correct for the study duration.

Haber's Law: Cⁿ* t = k, where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')^0.333333. C' is the sought concentration.

C' = 41.8 mg/m³ x (6h/0.25h)^0.3333333= 120.57 mg/m³.

The concentration of 120.57 mg/m³ was adjusted for the differences in the respiratory rates by normal conditions and by light activity: 0.21 m³/0.3125 m³

NOAEC corrected = 120.57 mg/m³ * 0.21 m³/0.3125 m³ = 81.024 mg/m³

AF for dose response relationship:

1

Justification:

default

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling not applicable for inhalation

AF for other interspecies differences:

2.5

Justification:

Default

AF for intraspecies differences:

5

Justification:

Default for workers

AF for the quality of the whole database:

2

Justification:

Study was conducted on a read-across substance

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.18 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

Value:

9.19 µg/m³

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

The default AF of 6 for study duration differences normally applicable (subacute - chronic) in this case was replaced here by the AF of 2 for study duration (subchronic-chronic), as the local effects occurring at the immediate port of entry are not considered to be correlating to such an extent with the exposure duration. Instead the local effects are considered to appear consistently already after fewer repetitions. Therefore, it is considered appropriate to use the Assessment factor of 2 in this case.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling is applied

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

default for workers

AF for the quality of the whole database:

1

Justification:

Good quality of data base

AF for remaining uncertainties:

1

Justification:

No further remaining uncertainties need to be taken into account

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.46 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

245.98 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEL of 2500 ppm (equivalent to 175.7 mg/kg/day) was determined for the substance tin chloride (CAS no. 7772-99-8) in an oral sub-chronic repeated-dose toxicity study in rats (OECD TG 408, GLP). This value was converted into the corrected dermal NOAEC taking into account the absorption rates (oral 100 %, dermal 100 %) and the correction factor between human and experimental exposure conditions workers (5 working days vs. 7 days continuous exposure) of 1.4.

 

NOAEC corrected = 175.7 mg/kg bw/day * 100/100 * 1.4 = 245.98 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Default (sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rats

AF for other interspecies differences:

2.5

Justification:

Default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans

AF for intraspecies differences:

5

Justification:

Default for workers

AF for the quality of the whole database:

1

Justification:

The quality of the database is considered to be good. No assessment factor for read-across is deemed nessecary, as it was fully agreed by ECHA in the decision letter, that data generated with tin sulphate can be used for evaluating the hazard of tin(II) chloride and vice versa.

AF for remaining uncertainties:

1

Justification:

default (no remaining uncertainties are identified)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.46 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

DNEL extrapolated from long term DNEL

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

245.98 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The short-term hazard is covered by the long-term DNEL.

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.53 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

76.39 mg/m³

Explanation for the modification of the dose descriptor starting point:

There is experimental data for sub-chronic repeated dose toxicity available by the oral and inhalatory route, of tin chloride or tin monoxide respectively. The long-term DNEL is derived from the repeated oral and repeated inhalation toxicity study. The DNEL considered the most appropriate is then selected.

Repeated dose via oral route as starting point

A NOAEL of 2500 ppm (equivalent to 175.7 mg/kg/day) was determined for the substance tin chloride (CAS no. 7772-99-8) in an oral sub-chronic repeated-dose toxicity study in rats (OECD TG 408, GLP). This value was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/1.15 m³/kg/day, the absorption rates (oral 50 %, inhalation 100 %; in accordance with ECHA Guidance R.8 the absorption rate of the starting route is half that of the end route).

 

NOAEC corrected = 175.7 mg/kg bw/day * 1/1.15 m³/kg/day * 50/100 = 76.39 mg/m³

Repeated dose via inhalation as starting point

A NOAEL of 9.19 µg/L (9.19 mg/m³) was determined in a repeated dose inhalation study on tin monoxide (OECD 412, GLP).

The NOAEL was converted into inhalatory NOAEC for duration of exposure (6h exposure in animal study versus 24h exposure for general population).

The bioavailability between experimental animals and humans at the relevant level of exposure is assumed to be the same; therefore no further correction was necessary.

As such, the corrected NOAEC was derived as follows:

 

NOAEC corrected= 9.19 mg/m³ * (6h/24h) = 2.3 mg/m³

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Default (sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling should be applied in case of oral-to-inhalation extrapolation

AF for other interspecies differences:

2.5

Justification:

default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans

AF for intraspecies differences:

10

Justification:

default for general population

AF for the quality of the whole database:

1

Justification:

The quality of the database is considered to be good. No additional assessment factor due to the use of read-across data is deemed nessecary, as it was fully agreed by ECHA in the decision letter, that data generated with tin sulphate can be used for evaluating the hazard of tin(II) chloride and vice versa.

AF for remaining uncertainties:

1

Justification:

default (no remaining uncertainties are identified)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.41 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEC

Value:

41.8 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

120.57 mg/m³

Explanation for the modification of the dose descriptor starting point:

The substance was classified as inhal. Acute Tox 4 (H332) based on an inhalation acute toxicity study on stannous oxalate (inhalative LC0 = 0.5 mg/L = 500 mg/m³), OECD TG 436, Dreher 2012). Furthermore, there is a 5 -day inhalation preliminary toxicity study with tin monoxide available, which was designed to assess the systemic toxic potential of tin monoxide in a 1 week (6 hours per day, 5 days a week) inhalation study in RccHan™;WIST rats. In the following the repeated dose toxicity study via inhalation according to OECD 412 had been conducted.

The inhalative NOAEL of 41.8 mg/m³ of the preliminary Dose-range finder for the 28 -day study was selected as the dose descriptor starting point for DNEL derivation. It was converted into a corrected inhalatory NOAEC by applying the Haber's Law to correct for the study duration.

Haber's Law: Cⁿ* t = k, where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')^0.333333. C' is the sought concentration.

C' = 41.8 mg/m³ x (6h/0.25h)^0.3333333= 120.57 mg/m³.

NOAEC corrected = 120.57 mg/m³

AF for dose response relationship:

1

Justification:

default

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling not applicable for inhalation

AF for other interspecies differences:

2.5

Justification:

Default

AF for intraspecies differences:

10

Justification:

Default for general population

AF for the quality of the whole database:

2

Justification:

Study was conducted on a read-across substance

AF for remaining uncertainties:

1

Justification:

Default

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.046 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor:

NOAEC

Value:

9.19 µg/m³

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

The default AF of 6 for study duration differences normally applicable (subacute - chronic) in this case was replaced here by the AF of 2 for study duration (subchronic-chronic), as the local effects occurring at the immediate port of entry are not considered to be correlating to such an extent with the exposure duration. Instead the local effects are considered to appear consistently already after fewer repetitions. Therefore, it is considered appropriate to use the Assessment factor of 2 in this case.

AF for interspecies differences (allometric scaling):

1

Justification:

Default

AF for other interspecies differences:

2.5

Justification:

detault

AF for intraspecies differences:

10

Justification:

default for general population

AF for the quality of the whole database:

1

Justification:

Good quality of data base

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEL of 2500 ppm (equivalent to 175.7 mg/kg/day) was determined for the substance tin chloride (CAS no. 7772-99-8) in a sub-chronic repeated-dose toxicity study (oral) in rats (OECD TG 408, GLP). This value does not have to be corrected, as the dermal and oral absorption rates are both considered to be 100 % as a worst-case assumption.

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Default (sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rats

AF for other interspecies differences:

2.5

Justification:

default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans

AF for intraspecies differences:

10

Justification:

Default for general population

AF for the quality of the whole database:

1

Justification:

The quality of the database is considered to be good. No assessment factor for read-across is deemed nessecary, as it was fully agreed by ECHA in the decision letter, that data generated with tin sulphate can be used for evaluating the hazard of tin(II) chloride and vice versa.

AF for remaining uncertainties:

1

Justification:

default (no remaining uncertainties are identified)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

DNEL extrapolated from long term DNEL

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The short-term hazard is covered by the long term DNEL.

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

175.7 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEL of 2500 ppm (equivalent to 175.7 mg/kg/day) was determined for the substance tin chloride (CAS no. 7772-99-8) in a sub-chronic repeated-dose toxicity study (oral) in rats (OECD TG 408, GLP). This value does not have to be corrected, as the oral absorption rates in human and rat are considered to be identical.

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Default (sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rat

AF for other interspecies differences:

2.5

Justification:

default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans

AF for intraspecies differences:

10

Justification:

Default for general population

AF for the quality of the whole database:

1

Justification:

The quality of the database is considered to be good. No assessment factor for read-across is deemed nessecary, as it was fully agreed by ECHA in the decision letter, that data generated with tin sulphate can be used for evaluating the hazard of tin(II) chloride and vice versa.

AF for remaining uncertainties:

1

Justification:

default (no remaining uncertainties are identified)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)