Tin sulphide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

35.26 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

881.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on the repeated exposure by inhalation. A conservative approach is used assuming a 50 % absorption rate via the oral route (end route) as compared to the inhalation route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

10 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal absorption. Oral absorption and dermal absorption were considered to be 5%.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further aassessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

The DNEL derivation is based on the NOAEL from an oral 90-day study with tin sulfide.

 

Long term exposure- systemic effect

Inhalation exposure

A subchronic or a subacute repeated dose toxicity test via inhalation exposure with tin sulfide is not available. Consequently, a subchronic oral toxicity study was used to derive the worker DNEL (long-term inhalation exposure). The study revealed a NOAEL > 1000 mg/kg bw/day.

 

Correction of the dose descriptor:

Oral NOAEL: > 1000 mg/kg bw/day

sRV(rat): 0.38 m3/ kg bw (8 hours) [standard respiratory volume of the rat]

ABS oral (rat)/ ABS inhalation (human): 0.5 [ratio of oral absorption in the rat to inhalative absorption in the human]

sRV (human)/ wRV (human): 6.7 m3/ 10 m3= 0.67 m3 [ratio of human standard respiratory volume to worker respiratory volume]

The oral NOAEL > 1000 mg/kg bw/ day is converted in an inhalation NOAEC > 881.6 mg/ m3.  

 

Calculation of the worker DNEL:

Corrected inhalatory NOAEC for worker: > 881.6 mg/ m3

Assessment factor for exposure duration (subchronic to chronic): 2

Assessment factor for intraspecies differences (worker): 5

Assessment factor for other interspecies differences: 2.5

Worker DNEL (inhalation exposure) = 881.6 mg/m3/ (1 x 2 x 1 x 5 x 2.5 x 1 x 1) = 881.6 / 25 = 35.26 mg/ m3  

 

Dermal exposure

A subchronic or a subacute dermal repeated dose toxicity test with tin sulfide is not available. Consequently, a subchronic oral toxicity study was used to derive the worker DNEL (long-term dermal exposure). The study revealed a NOAEL > 1000 mg/kg bw/day.

 

Considering the appropriate assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:  

Correction of the dose descriptor:

Dose descriptor of relevant study: 1000 mg/kg bw/day (NOAEL x 1; assuming 5 % dermal absorption and 5 % oral absorption)

 

Assessment factor for exposure duration (subchronic to chronic): 2

Allometric scaling factor (rat to human): 4

Assessment factor for other interspecies differences: 2.5

Assessment factor for intraspecies differences (worker): 5 

Taking the above mentioned assessment factors into account, the following worker DNEL is:

Worker DNEL (dermal exposure) =  1000 mg/kg bw/day / (1 x 2 x 4 x 2.5 x 5 x 1 x 1) = 1000 /100 = 10 mg/kg bw/day  

 

Acute/ short term exposure- systemic effect

Inhalation

There is no indication for acute systemic toxicity of tin sulfide. The substance is not classified for inhalation toxicity. Moreover, due to its strong adhesive properties tin sulfide particles agglomerate and deposit. The vapour pressure is negligible. Taken together, its physicochemical properties exclude inhalative exposure. Also no peak exposure is expected. Therefore no DNEL is required.

 

Dermal

In an acute dermal toxicity study with tin sulfide according EU method B.3 and OECD 402, a LD50 value of > 2000 mg/kg bw was obtained. Thus, the test material is not classified and labelled for acute dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL was derived.

 

Acute/ short term exposure- systemic effect

Inhalation

There is no indication for acute systemic toxicity of tin sulfide. The substance is not classified for inhalation toxicity. Moreover, due to its strong adhesive properties tin sulfide particles agglomerate and deposit. The vapour pressure is negligible. Taken together, its physicochemical properties exclude inhalative exposure. Also no peak exposure is expected. Therefore no DNEL is required.

 

Dermal

In an acute dermal toxicity study with tin sulfide according EU method B.3 and OECD 402, a LD50 value of > 2000 mg/kg bw was obtained. Thus, the test material is not classified and labelled for acute dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL was derived.

 

Acute and long term exposure- local effect

Respiratory irritation

Due to its strong adhesive properties tin sulfide particles agglomerate and deposit. The vapour pressure is negligible. Taken together, its physicochemical properties excludes inhalative exposure. Moreover, there is no indication for any adverse local effects as the substance is neither classified for inhalation toxicity nor for irritation/corrosion according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL is required.

 

 

 

Skin irritation

The test item is not classified for skin irritation/corrosion and skin sensitization according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL was derived.  

 

Eye irritation

The test item is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).

 

References

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19–N.

- ECETOC (2010). Technical Report 110.Guidance on assessment factors to derive a DNEL. according to Annex VI of Regulation EC 1272/2008 (CLP).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.7 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

437.8 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on the repeated exposure by inhalation. A conservative approach is used assuming a 50 % absorption rate via the oral route (end route) as compared to the inhalation route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

5 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal absorption. Based on the
physiochemical properties it is assumed that the test item's absorption corresponds to 10 % of the
oral uptake.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

5 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further aassessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General

The DNEL derivation is based on the NOAEL from an oral 90-day study with tin sulfide.

 

Long term exposure- systemic effect

Inhalation exposure

A subchronic or a subacute repeated dose toxicity test via inhalation exposure with tin sulfide is not available. Consequently, a subchronic oral toxicity study was used to derive the worker DNEL (long-term inhalation exposure). The study revealed a NOAEL > 1000 mg/kg bw/day.

 

Correction of the dose descriptor:

Oral NOAEL: > 1000 mg/kg bw/day

sRV(rat): 1.15 m3/ kg bw (24 hours) [standard respiratory volume of the rat]

ABS oral (rat)/ ABS inhalation (human): 0.5 [ratio of oral absorption in the rat to inhalative absorption in the human]

The oral NOAEL > 1000 mg/kg bw/ day is converted in an inhalation NOAEC > 437.8 mg/ m3.  

Calculation of the consumer DNEL:

Corrected inhalatory NOAEC for consumer: > 437.8 mg/ m3

Assessment factor for exposure duration (subchronic to chronic): 2

Assessment factor for intraspecies differences (consumer): 10 

Assessment factor for other interspecies differences: 2.5

Consumer DNEL (inhalation exposure) = 437.8 mg/m3/ (1 x 2 x 1 x 10 x 2.5 x 1 x 1) = 437.8 / 50 = 8.7 mg/ m3  

 

 

 

Dermal exposure

A subchronic or a subacute dermal repeated dose toxicity test with tin sulfide is not available. Consequently, a subchronic oral toxicity study was used to derive the worker DNEL (long-term dermal exposure). The study revealed a NOAEL > 1000 mg/kg bw/day.

 

Correction of the dose descriptor:

Dose descriptor of relevant study: 1000 mg/kg bw/day (NOAEL x 1; assuming 5 % dermal absorption and 5 % oral absorption)

Assessment factor for exposure duration (subchronic to chronic): 2

Allometric scaling factor (rat to human): 4

Assessment factor for other interspecies differences: 2.5

Assessment factor for intraspecies differences (consumer): 10 

Taking the above mentioned assessment factors into account, the following consumer DNEL is:

Consumer DNEL (dermal exposure) = 1000 mg/kg bw/day / (1 x 2 x 4 x 2.5 x 10 x 1 x 1) = 1000 / 200 = 5.0 mg/kg bw/day  

 

Oral exposure

A subchronic oral repeated dose toxicity test with tin sulfide revealed a NOAEL > 1000 mg/kg bw/day.

 

Considering the appropriate assessment factors, the consumer DNEL (long-term oral exposure) is calculated as follows:  

Correction of the dose descriptor:

Oral NOAEL: > 1000 mg/kg bw/day

Assessment factor for exposure duration (subchronic to chronic): 2

Allometric scaling factor (rat to human): 4

Assessment factor for other interspecies differences: 2.5

Assessment factor for intraspecies differences (consumer): 10 

Taking the above mentioned assessment factors into account, the following consumer DNEL is:

Consumer DNEL (oral exposure) = 1000 mg/kg bw/day / (1 x 2 x 4 x 2.5 x 10 x 1 x 1) = 1000 / 200 = 5.0 mg/kg bw/day

 

Acute/ short term exposure- systemic effect

Inhalation

There is no indication for acute systemic toxicity of tinsulfide. The substance is not classified for inhalation toxicity. Moreover, due to its strong adhesive properties tin sulfide particles agglomerate and deposit. The vapour pressure is negligible. Taken together, its physicochemical properties exclude inhalative exposure. Also no peak exposure is expected. Therefore no DNEL is required.

 

Dermal

In an acute dermal toxicity study with tin sulfide according EU method B.3 and OECD 402, a LD50 value of > 2000 mg/kg bw was obtained. Thus, the test material is not classified and labelled for acute dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL wasderived.

 

Oral

There is no indication for acute systemic toxicity of tin sulfide. Based on the physical form and low water solubility, but mainly on the absence of toxicity in acute and repeated dose oral toxicity studies, oral absorption of tin sulfide is assumed to be very low. Therefore no DNEL is derived.

 

Acute and long term exposure- local effect

Respiratory irritation

Due to its strong adhesive properties tin sulfide particles agglomerate and deposit. The vapour pressure is negligible. Taken together, its physicochemical properties exclude inhalative exposure. Moreover, there is no indication for any adverse local effects as the substance is neither classified for inhalation toxicity nor for irritation/corrosion according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL is required.

 

Skin irritation

The test item is not classified for skin irritation/corrosion and skin sensitization according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Therefore no DNEL was derived.  

 

Eye irritation

The test item is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).

 

References

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19–N.