Dibismuth trisulphide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

48.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

45

Modified dose descriptor starting point:

NOAEC

Value:

2 169 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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:

3

Justification:

Intraspecies differences of workers are considered to be fully covered by the selected factor according to ECETOC Technical Report No. 110.

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:

137 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

180

Modified dose descriptor starting point:

NOAEL

Value:

24 600 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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:

3

Justification:

An intraspecies difference factor of 3 for workers is considered to be sufficient (ECETOC Technical Report No. 110).

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

No respective experimental data for dibismuth trisulfide are available. Consequently, read-across was applied using study results from bismuth. The DNEL derivation is based on the calculated NOAEL for dibismuth trisulfide.

DNEL derivation is performed under consideration of the recommendations of ECHA REACH Guidance (2010) and ECETOC (2010). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1.  

Long term exposure- systemic effect

Inhalation exposure

A subchronic and a subacute repeated dose toxicity test with dibismuth trisulfide are not available. Consequently, read-across was applied using study results from bismuth in order to derive the worker DNEL (long-term inhalation exposure). A 28-day repeated dose oral toxicity study with bismuth revealed a NOAEL > 1000 mg Bismuth/kg bw/day. The DNEL derivation is based on the calculated NOAEL > 2460 mg/kg bw/day for dibismuth trisulfide.  

Correction of the dose descriptor:

Oral NOAEL: > 2460 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 > 2460 mg/kg bw/ day is converted in an inhalation NOAEC > 2169 mg/ m3.  

Calculation of the worker DNEL:

Corrected inhalatory NOAEC for worker: > 2169 mg/ m3

Assessment factor for exposure duration (subacute to chronic): 6

Assessment factor for intraspecies differences (worker): 3 

Assessment factor for other interspecies differences: 2.5

Worker DNEL (inhalation exposure) = 2169 mg/m3/ (1 x 6 x 1 x 3 x 2.5 x 1 x 1) = 2169 / 45 = 48.2 mg/ m3  

Dermal exposure

A subchronic and a subacute repeated dose toxicity test with dibismuth trisulfide are not available. Consequently, read-across was applied using study results from bismuth in order to derive the worker DNEL (long-term dermal exposure). A 28-day repeated dose oral toxicity study with bismuth revealed a NOAEL > 1000 mg Bismuth/kg bw/day. The DNEL derivation is based on the calculated NOAEL > 2460 mg/kg bw/day for dibismuth trisulfide.

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: > 24600 mg/kg bw/day (NOAEL x 10; assuming 10 % dermal absorption)

Assessment factor for exposure duration (subacute to chronic): 6

Allometric scaling factor (rat to human): 4

Assessment factor for other interspecies differences: 2.5

Assessment factor for intraspecies differences (worker): 3 

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

Worker DNEL (dermal exposure) = 24600 mg/kg bw/day / (1 x 6 x 4 x 2.5 x 3 x 1 x 1) = 24600 / 180 = 137 mg/kg bw/day  

Acute/ short term exposure- systemic effect

Inhalation

There is no indication for acute systemic toxicity of dibismuth trisulfide. The substance is not classified for inhalation toxicity. Moreover, due to its strong adhesive properties dibismuth trisulfide 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 dibismuth trisulfide 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 dibismuth trisulfide 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:

14.46 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):

150

Modified dose descriptor starting point:

NOAEC

Value:

2 169 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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:

41 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):

600

Modified dose descriptor starting point:

NOAEL

Value:

24 600 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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:

4.1 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):

600

Modified dose descriptor starting point:

NOAEL

Value:

2 460 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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

No respective experimental data for dibismuth disulfide are available. Consequently, read-across was applied using study results from bismuth. The DNEL derivation is based on the calculated NOAEL for dibismuth trisulfide.

DNEL derivation is performed under consideration of the recommendations of ECHA REACH Guidance (2010). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1.  

Long term exposure- systemic effect

Inhalation exposure

A subchronic and a subacute repeated dose toxicity test with dibismuth trisulfide are not available. Consequently, read-across was applied using study results from bismuth in order to derive the consumer DNEL (long-term inhalation exposure). A 28-day repeated dose oral toxicity study with bismuth revealed a NOAEL > 1000 mg Bismuth/kg bw/day. The DNEL derivation is based on the calculated NOAEL > 2460 mg/kg bw/day for dibismuth trisulfide.  

Correction of the dose descriptor:

Oral NOAEL: > 2460 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 > 2460 mg/kg bw/ day is converted in an inhalation NOAEC > 1070 mg/ m3.  

Calculation of the consumer DNEL:

Corrected inhalatory NOAEC for consumer: > 1070 mg/ m3

Assessment factor for exposure duration (subacute to chronic): 6

Assessment factor for intraspecies differences (consumer): 10 

Assessment factor for other interspecies differences: 2.5

Consumer DNEL (inhalation exposure) = 1070 mg/m3/ (1 x 6 x 1 x 10 x 2.5 x 1 x 1) = 1070 / 150 = 7.13 mg/ m3  

Dermal exposure

A subchronic and a subacute repeated dose toxicity test with dibismuth trisulfide are not available. Consequently, read-across was applied using study results from bismuth in order to derive the consumer DNEL (long-term dermal exposure). A 28-day repeated dose oral toxicity study with bismuth revealed a NOAEL > 1000 mg Bismuth/kg bw/day. The DNEL derivation is based on the calculated NOAEL > 2460 mg/kg bw/day for dibismuth trisulfide.

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

Correction of the dose descriptor:

Dose descriptor of relevant study: > 24600 mg/kg bw/day (NOAEL x 10; assuming 10 % dermal absorption)

Assessment factor for exposure duration (subacute to chronic): 6

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) = 24600 mg/kg bw/day / (1 x 6 x 4 x 2.5 x 10 x 1 x 1) = 24600 / 600 = 41 mg/kg bw/day  

Oral exposure

A subchronic and a subacute repeated dose toxicity test with dibismuth trisulfide is not available. Consequently, read-across was applied using study results from bismuth in order to derive the consumer DNEL (long-term oral exposure). A 28-day repeated dose oral toxicity study with bismuth revealed a NOAEL > 1000 mg Bismuth/kg bw/day. The DNEL derivation is based on the calculated NOAEL > 2460 mg/kg bw/day for dibismuth trisulfide.

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

Correction of the dose descriptor:

Oral NOAEL: > 2460 mg/kg bw/day

Assessment factor for exposure duration (subacute to chronic): 6

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) = 2460 mg/kg bw/day / (1 x 6 x 4 x 2.5 x 10 x 1 x 1) = 2460 / 600 = 4.1 mg/kg bw/day

Acute/ short term exposure- systemic effect

Inhalation

There is no indication for acute systemic toxicity of dibismuth trisulfide. The substance is not classified for inhalation toxicity. Moreover, due to its strong adhesive properties dibismuth trisulfide 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 dibismuth trisulfide 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.

Oral

There is no indication for acute systemic toxicity of dibismuth trisulfide. 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 dibismuth trisulfide is assumed to be very low. This conclusion is confirmed by the literature on oral absorption of insoluble bismuth compounds. Therefore no DNEL is derived.

Acute and long term exposure- local effect

Respiratory irritation

Due to its strong adhesive properties dibismuth trisulfide 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.