Pentapotassium bis(peroxymonosulphate) bis(sulphate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.112 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

Value:

1.4 mg/m³

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:

1

Justification:

Local effects are independent from time.

AF for interspecies differences (allometric scaling):

1

Justification:

Local effects are independent from metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4 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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

400 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no experimental data on repeated dermal exposure. Based on the physicochmical properties, especially the low log Pow value (<0), dermal absorption is anticipated to be low. However, the substance is corrosive to skin, which may enhance penetration. Therefore a dermal absorption rate of 50 % of the oral absorption rate was taken for calculation.

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:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

General - Worker

DNEL derivation for the substance is performed under consideration of the recommendations of ECHA REACH Guidance (2012). In view of the data used for evaluation, the "quality of whole database factors" and the “factor for remaining uncertainties“ is considered to amount to a value of 1.

 

Short-term, local DNEL

The skin and eye irritation and sensitization potential of the test item was assessed in several studies. The test item demonstrated to be corrosive to skin and causing serious damage to the eyes. Thus, a qualitative risk assessment was performed.

 

Short-term, systemic DNEL

The guidance on dose/concentration response regarding human health (section R.8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard according to Regulation (EC) No 1272/2008 (CLP). As this substance is not classified for short-term inhalative or dermal systemic effects, no acute systemic DNELs need to be calculated for those exposure routes.

 

Long-term, local DNEL

Inhalation exposure

A subacute inhalation toxicity study revealed no effects with regard to the respiratory tract, but based on local findings in the eyes a NOAEC of 1.4 mg/m³ is identified as the relevant dose descriptor and starting point for DNEL calculation. A long-term inhalation DNEL for local effects is derived.

 

Assessment factors:

Dose response differences: 1

Differences in exposure duration: 1

Interspecies differences (allometric scaling): 1

Other interspecies differences: 2.5

Intraspecies differences (worker): 5

Taking the above mentioned assessment factors into account, the following worker long-term inhalation DNEL for local effects is:

1.4 mg/m³ / (1 x 1 x 2.5 x 5) =10.3 mg/m³ / 12.5

= 0.112 mg/m³

 

Dermal exposure

The skin irritation and sensitization potential of the test item was assessed in several in vivo studies. The test item demonstrated to be corrosive to skin and causing serious damage to the eyes. Thus, a qualitative risk assessment was performed.

 

Long-term, systemic DNEL

Inhalation exposure

In the subacute repeated dose toxicity study, the substance caused primary local toxicity effects. All observed systemic effects were of secondary nature.  Therefore no DNEL, systemic, long-term was derived for inhalation. The systemic exposure is sufficiently covered by the long-term local DNEL.

 

Dermal exposure

In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90 d repeated dose oral toxicity study (200 mg/kg bw/d) is identified as the relevant dose descriptor.

Modification into a correct starting point:

Correction for dermal absorption rates of the test substance (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12): Dermal absorption is supposed to be low for several reasons: With a low log Pow (below 0) and a water solubility above 10 g/L the substance is to hydrophilic to cross the lipid rich environment of the stratum corneum. Thus, dermal uptake is anticipated to be low. In addition, the results of the acute dermal toxicity support a low absorption via dermal route. Nonetheless the substance causes skin corrosion. Therefore, dermal absorption was calculated to be 50% of oral absorption.

In conclusion, dermal NOAEL = oral NOAEL x 100/50 =

200 x (100/50) = 400 mg/kg bw/d.

 

Assessment factors:

Dose response differences: 1

Differences in exposure duration: 2

Interspecies differences (allometric scaling): 4

Remaining interspecies differences: 2.5

Intraspecies differences (worker): 5

Taking the above mentioned assessment factors into account, the following worker long- term dermal DNEL for systemic effects is:

400 mg/kg bw/d / (1 x 2 x 4 x 2.5 x 5) = 400 mg/kg bw/day / 100

= 4 mg/kg bw/day

 

 

References

- ECHA (2012). 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 –EN.

- ECHA (2016). Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation. Version 3. ECHA-2016-G-04-EN

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.056 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:

1.4 mg/m³

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:

1

Justification:

Local effects are independent from time.

AF for interspecies differences (allometric scaling):

1

Justification:

Local effects are independent from metabolic rate.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the more heterogenous group "general population" is used.

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

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

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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

400 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A low dermal absorption value can be expected due to the physico- chemical properties However the substance shows skin corrosive properties. Therefore, dermal absorption is anticipated to be 50 % of oral absorption.

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:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the more heterogenous group "general population" is used.

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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

200

Dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

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:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the more heterogenous group "general population" is used.

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:

DNEL (Derived No Effect Level)

Value:

3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

0.33

DNEL extrapolated from long term DNEL

Modified dose descriptor starting point:

LOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

General

DNEL derivation for the substance 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 the “factor for remaining uncertainties“ is considered to amount to a value of 1.

 

Short-term, local DNEL

The skin and eye irritation and sensitization potential of the test item was assessed in several studies. The test item demonstrated to be corrosive to skin and causing serious damage to the eyes. Thus, a qualitative risk assessment was performed.

 

Short-term, systemic DNEL

The guidance on dose/concentration response regarding human health (section R.8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard according to Regulation (EC) No 1272/2008 (CLP). As this substance is not classified for short-term inhalative or dermal systemic effects, no acute systemic DNELs need to be calculated for those exposure routes.

The substance is classified as harmful if swallowed (H302). Thus, short term oral DNEL is derived for the general population taking the long-term DNEL as basis.

 

Long-term, local DNEL

Inhalation exposure

A subacute inhalation toxicity study revealed no effects with regard to the respiratory tract, but based on local findings in the eyes a NOAEC of 1.4 mg/m³ is identified as the relevant dose descriptor and starting point for DNEL calculation. A long-term inhalation DNEL for local effects is derived.

 

Assessment factors:

Dose response differences: 1

Differences in exposure duration: 1

Interspecies differences (allometric scaling): 1

Other interspecies differences: 2.5

Intraspecies differences (general population): 10

Taking the above mentioned assessment factors into account, the following worker long-term inhalation DNEL for local effects is:

1.4 mg/m³ / (1 x 1 x 2.5 x 10) =1.4 mg/m³ / 25

= 0.056 mg/m³

 

Dermal exposure

The skin irritation and sensitization potential of the test item was assessed in several in vivo studies. The test item demonstrated to be corrosive to skin and causing serious damage to the eyes. Thus, a qualitative risk assessment was performed.

 

Long-term, systemic DNEL

Inhalation exposure

In the subacute repeated dose toxicity study, the substance caused primary local toxicity effects. All observed systemic effects were of secondary nature.  Therefore no DNEL, systemic, long-term was derived for inhalation. The systemic exposure is sufficiently covered by the long-term local DNEL.

 

Dermal exposure

In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90 d repeated dose oral toxicity study (200 mg/kg bw/d) is identified as the relevant dose descriptor.

Modification into a correct starting point:

Correction for dermal absorption rates of the test substance (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12): Dermal absorption is supposed to be low for several reasons: With a low log Pow (below 0) and a water solubility above 10 g/L the substance is to hydrophilic to cross the lipid rich environment of the stratum corneum. Thus, dermal uptake is anticipated to be low. In addition, the results of the acute dermal toxicity support a low absorption via dermal route. Nonetheless the substance causes skin corrosion. Therefore, dermal absorption was calculated to be 50% of oral absorption.

In conclusion, dermal NOAEL = oral NOAEL x 100/50 =

200 x (100/50) = 400 mg/kg bw/d.

 

Assessment factors:

Dose response differences: 1

Differences in exposure duration: 2

Interspecies differences (allometric scaling): 4

Remaining interspecies differences: 2.5

Intraspecies differences (general population): 10

Taking the above mentioned assessment factors into account, the following worker long- term dermal DNEL for systemic effects is:

400 mg/kg bw/d / (1 x 2 x 4 x 2.5 x 10) = 400 mg/kg bw/day / 200

= 2 mg/kg bw/day

 

Oral exposure

In order to derive the general population DNEL (long-term oral exposure), the NOAEL assessed in the subchronic repeated dose oral toxicity study (200 mg/kg bw/d) is identified as the relevant dose descriptor. No modification of the starting point is necessary.

 

Assessment factors:

Dose response differences: 1

Differences in exposure duration: 2

Interspecies differences (allometric scaling): 4

Remaining interspecies differences: 2.5

Intraspecies differences (general population): 10

Taking the above mentioned assessment factors into account, the following worker long- term dermal DNEL for systemic effects is:

200 mg/kg bw/d / (1 x 2 x 4 x 2.5 x 10) = 200 mg/kg bw/day / 200

= 1 mg/kg bw/day

 

References

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. ECHA-2010 -G-19 –EN.

- ECHA (2016). Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation. Version 3. ECHA-2016-G-04-EN