DS-2920A-E

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

3

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

The test substance Benzoic acid, 4-[2-(2-hydroxy-6-sulfo-1-naphthalenyl)diazenyl]-, strontium salt (2:1), is a solid dyestuff. Based on the available data, classification for toxicity is not warranted under Regulation (EC) No.1272/2008 (CLP). No hazard for human health was identified.

Therefore, only long-term DNELs for the primary routes of exposure were derived. The primary routes of anticipated industrial exposure to the substance may occur via inhalation and skin contact. However, peak exposure values were not expected, due to the low vapour pressure and the relatively high particle size.

There are no data available concerning repeated dose toxicity for the test item. Therefore, a read across to the test item 1-Naphthalenesulfonic acid, 2-[2-(2-hydroxy-6-sulfo-1-naphthalenyl)diazenyl]-, strontium salt (1:1), EC No. 427 -930 -3 was performed.

Using the rat oral subacute repeated dose study conducted with the analogous substance according to OECD Guideline 407 (BASF SE, Testing Lab.: Safepharm Laboratories Ltd 1999), the NOAEL for general, systemic toxicity of the test substance was set to ≥ 1000 mg/kg bw/d for male and female rats, the highest dose tested.

This NOAEL was taken as the point of departure for DNEL derivation for long-term exposure following dermal and inhalation contact.

 

Dermal long-term exposure – systemic effects:

For derivation of the dermal DNEL, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8.

The test item is moderately soluble in water and biotransformation is expected. Due to the low partition coefficient log Pow, limited adsorption is expected. However, due to ionisable groups of the test item absorption could be affected by pH.

Assuming comparable absorption for the dermal and the oral route an assessment factor of 1.0 was used and the oral NOAEL was converted into a dermal NOAEL of 1000 mg/kg bw/d.

 

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

• Interspecies factor: 4

As interspecies factor for the correction for differences in metabolic rate between rat and humans (allometric factor) the default factor of 4 was used as recommended both by the REACh Guidance Document Chapter R.8 and the ECETOC TR 110.

 

• Intraspecies factor: 3

Concerning the intraspecies factor, an assessment factor of 3 as recommended by the ECETOC TR 110 was deemed as sufficient. Therefore, for the derivation of an occupational DNEL an AF of 3 is considered appropriate.

 

• Exposure duration: 1

In the absence of an effect, extrapolation to longer exposure times that may cause effect enhancement is not warranted.

 

• Remaining differences: 1

No additional assessment factor for remaining differences was deemed necessary as presented in detail in the ECETOC TR 110.

 

• Dose-response: 1 (default)

 

• Quality of whole database: 1 (default). Based on the use of the NOAEL set as greater than 1000 mg/kg bw/d (maximal dose tested) as dose descriptor, an additional AF to address the uncertainty of using an read across from a structurally related substance is not considered.

 

Total AF = 4 x 3 x 1 = 12

 

Based on this calculation the resulting DNEL for dermal exposure is 83 mg/kg bw/d.

Inhalation long-term exposure – systemic effects:

For derivation of the inhalative DNEL, allometric scaling was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8.

Thereby, the oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg bw/d x 6.7 m³/10 m³). The substance is a non-volatile powder with only a small proportion of particles of respirable particle size, a significant inhalation exposure is not anticipated. As recommended by the ECETOC TR 110, no additional assessment factor for differences between oral absorption in rats and inhalative absorption in humans was used. The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 1763 mg/m³.

 

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

 

• Interspecies factor: 1

As recommended by the ECETOC TR 110, besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to humans as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

 

• Intraspecies factor: 3

Concerning the intraspecies factor, an assessment factor of 3 as recommended by the ECETOC TR 110 was deemed as sufficient. Therefore, for the derivation of an occupational DNEL an AF of 3 is considered appropriate.

 

• Exposure duration: 1

In the absence of an effect, extrapolation to longer exposure times that may cause effect enhancement is not warranted.

 

• Dose-response: 1 (default)

 

• Quality of whole database: 1 (default). Based on the use of the NOAEL set as greater than 1000 mg/kg bw/d (maximal dose tested) as dose descriptor, an additional AF to address the uncertainty of using an read across from a structurally related substance is not considered.

 

Total AF = 1 x 3 x 1 = 3

 

Based on this calculation the resulting DNEL for inhalation is 588 mg/m³. Because this value exceeds the recommended value for inert dusts, the DNEL is limited to the general dust limit of 3 mg/m3 (respirable fraction).

 

 

DNEL calculation ist based on  

·        ECHA (2010). REACh Guidance Document R.8.

·        ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. ECETOC Technical Report No. 110.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

5

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

50 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

50 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

The test substance Benzoic acid, 4-[2-(2-hydroxy-6-sulfo-1-naphthalenyl)diazenyl]-, strontium salt (2:1), is a solid dyestuff. Based on the available data, classification for toxicity is not warranted under Regulation (EC) No.1272/2008 (CLP). No hazard for human health was identified.

Therefore, only long-term DNELs for the primary routes of exposure were derived. The primary routes of anticipated industrial exposure to the substance may occur via inhalation and skin contact. However, peak exposure values were not expected, due to the low vapour pressure and the relatively high particle size.

In addition, ingestion has to be considered for the general population.

 

There are no data available concerning repeated dose toxicity for the test item. Therefore, a read across to the structural similar test item 1-Naphthalenesulfonic acid, 2-[2-(2-hydroxy-6-sulfo-1-naphthalenyl)diazenyl]-, strontium salt (1:1), EC No. 427 -930 -3 was performed.

 

Using the oral subacute repeated dose study with rats conducted with the analogous substance according to OECD Guideline 407 (BASF SE, Testing Lab.: Safepharm Laboratories Ltd 1999), the NOAEL for general, systemic toxicity of the test substance was set to ≥ 1000 mg/kg bw/d for male and female rats, the highest dose tested.

This NOAEL was taken as the point of departure for DNEL derivation for long-term exposure following dermal, inhalation or oral exposure.

 

 

Dermal long-term exposure – systemic effects:

For derivation of the dermal DNEL, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8.

The test item is moderately soluble in water and biotransformation is expected. Due to the low partition coefficient log Pow, limited adsorption is expected. However, due to ionisable groups of the test item absorption could be affected by pH.

Assuming comparable absorption for the dermal and the oral route an assessment factor of 1.0 was used and the oral NOAEL was converted into a dermal NOAEL of 1000 mg/kg bw/d.

 

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

• Interspecies factor: 4

As interspecies factor for the correction for differences in metabolic rate between rat and humans (allometric factor) the default factor of 4 was used as recommended both by the REACh Guidance Document Chapter R.8 and the ECETOC TR 110.

 

• Intraspecies factor: 5

Concerning the intraspecies factor, for general population an assessment factor of 5 as recommended by the ECETOC TR 110 was deemed as sufficient.

 

• Exposure duration: 1

In the absence of an effect, extrapolation to longer exposure times that may cause effect enhancement is not warranted.

 

• Remaining differences: 1

No additional assessment factor for remaining differences was deemed necessary as presented in detail in the ECETOC TR 110.

 

• Dose-response: 1 (default)

 

• Quality of whole database: 1 (default). Based on the use of the NOAEL set as greater than 1000 mg/kg bw/d (maximal dose tested) as dose descriptor, an additional AF to address the uncertainty of using an read across from a structurally related substance is not considered.

 

Total AF = 4 x 5 x 1 = 20

 

Based on this calculation the resulting DNEL for dermal exposure is 50 mg/kg bw/d.

 

 

Inhalation long-term exposure – systemic effects:

The point of departure of 1000 mg/kg bw/d was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8:

Thereby, oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg bw/d). No additional assessment factor for differences between oral absorption in rats and inhalative absorption in humans was used. The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 870 mg/m³.

 

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

 

• Interspecies factor: 1

As recommended by the ECETOC TR 110, no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to humans as the rat's ventilation frequency is higher.

 

• Intraspecies factor: 5

An assessment factor of 5 as recommended by the ECETOC TR 110 was deemed as sufficient.

 

• Exposure duration: 1

In the absence of an effect, extrapolation to longer exposure times that may cause effect enhancement is not warranted.

 

• Dose-response: 1 (default)

 

• Quality of whole database: 1 (default). Based on the use of the NOAEL set as greater than 1000 mg/kg bw/d (maximal dose tested) as dose descriptor, an additional AF to address the uncertainty of using an read across from a structurally related substance is not considered.

Total AF = 1 x 5 x 1 = 5

 

Based on this calculation the resulting DNEL for inhalation is 174 mg/m³. Because this value exceeds the recommended value for inert dusts, the DNEL is limited to the general dust limit of 3 mg/m3 (respirable fraction).

 

 

Oral long-term exposure –systemic effects:

In addition, for general population, the DNEL for oral long-term exposure was derived.

Using the point of departure of 1000 mg/kg bw/d, the following assessment factors are taken into account for the final DNEL calculation for the oral route:

 

• Interspecies factor: 4

As interspecies factor for the correction for differences in metabolic rate (allometric factor) the default factor of 4 was used as recommended both by the REACh Guidance Document Chapter R.8 and the ECETOC TR 110.

 

• Intraspecies factor: 5

An assessment factor of 5 as recommended by the ECETOC TR 110 was deemed as sufficient.

 

• Exposure duration: 1

In the absence of an effect, extrapolation to longer exposure times that may cause effect enhancement is not warranted.

 

• Dose-response: 1 (default)

 

• Quality of whole database: 1 (default). Based on the use of the NOAEL set as greater than 1000 mg/kg bw/d (maximal dose tested) as dose descriptor, an additional AF to address the uncertainty of using an read across from a structurally related substance is not considered.

 

Total AF = 4 x 5 x 1 = 20

 

Based on this calculation the resulting DNEL for oral exposure is 50 mg/kg bw/d.

 

DNEL calculation is based on  

·    ECHA (2010). REACh Guidance Document Chapter R.8.

· ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. ECETOC Technical  Report No. 110.