Disodium 7-[[4,6-bis[(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[[4-[(4-sulphonatophenyl)azo]phenyl]azo]naphthalene-2-sulphonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.5 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):

75

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NAEC

Value:

1 763 mg/m³

Explanation for the modification of the dose descriptor starting point:

NAEC worker (8h) = (1000 mg/kg bw/0.38 m³/kg bw) * 6.7 m³/10 m³

[where: NAEC is the modified starting point; 1000 mg/kg bw is the NOAEL for repeated dose/reproductive/developmental toxicity; 0.38 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure; for workers a further correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. This correction factor derives from the inhalation volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity)]

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Scaling issues just evaluated in modified starting point

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

5

Justification:

Worker population

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

Based on a worst-case approach, 100 % adsorption for inhalation route for animal and human is assumed.

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:

3.3 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):

300

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric factor rat to man

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

5

Justification:

Worker population

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

Based on a worst-case approach, 100 % adsorption for dermal route for animal and human is assumed.

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

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

The Derived No Effect Level for inhalation long-term exposure is estimated from the No Observed Effect Level obtained from the combined repeated dose /reproductive-developmental toxicity experiment. The treatment did not produce changes detected in health condition control, except coloured faeces. Findings observed in both sexes, both parental and pups animals, were considered to be of no toxicological significance. No significant changes related to test substance administration were recorded up to the highest tested dose of 1000 mg/kg bw/day, which has been indicated as the NOAEL for both repeated dose toxicity and reproductive/developmental toxicity.

The calculation of DNELs is based on the NOAEL identified and has to be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the no observed effect level has to be corrected as mentioned below.

INHALATION ROUTE - Systemic effects long term exposure

Corrected starting point for the inhalation route for workers: NAEC worker (8h) = (1000 mg/kg bw/0.38 m³/kg bw) * (6.7 m³/ 10 m³)

[where: NAEC is the modified starting point; 1000 mg/kg bw is the NOAEL for repeated dose/reproductive/developmental toxicity); 0.38 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure; for workers a further correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. This correction factor derives from the inhalation volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity)]

Thus, the corrected starting point NAEC was estimated to be 1763 mg/m³.

Subsequently other assessment factors have been used to derived the DNEL:

- differences in duration of exposure 6, because the starting value resulted from a subacute study

- remaining differences 2.5

- intraspecies differences 5, for worker population

DERMAL ROUTE - Systemic effects long term exposure

Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral-to-dermal extrapolation, thus NOAEL has been used as starting point, without any further correction.

Subsequently other assessment factors have been used to derived the DNEL:

- differences in duration of exposure 6, because the starting value resulted from a subacute study

- because the NOAEL was recorded in a study conducted on rats, for interspecies differences the allometric scaling of 4 has been used

- remaining differences 2.5

- intraspecies differences 5, for worker population

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.8 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

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NAEC

Value:

870 mg/m³

Explanation for the modification of the dose descriptor starting point:

NAEC general population (24h) = 1000 mg/kg bw/1.15 m³/kg bw

[where: NAEC is the modified starting point; 1000 mg/kg bw is the NOAEL for repeated dose/reproductive/developmental toxicity; 1.15 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure]

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Scaling issues just evaluated in modified starting point

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

Based on a worst-case approach, 100 % adsorption for inhalation route for animal and human is assumed.

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:

1.7 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

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric factor rat to man

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

Based on a worst-case approach, 100 % adsorption for dermal route for animal and human is assumed.

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

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 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

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No default factor should be introduced when performing on the same route; 1000 mg/kg bw is the NOAEL for repeated dose/reproductive/developmental toxicity.

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric factor rat to man

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

100 % adsorption for oral route for animal and human is assumed.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The Derived No Effect Level for inhalation long-term exposure is estimated from the No Observed Effect Level obtained from the combined repeated dose /reproductive-developmental toxicity experiment. The treatment did not produce changes detected in health condition control, except coloured faeces. Findings observed in both sexes, both parental and pups animals, were considered to be of no toxicological significance. No significant changes related to test substance administration were recorded up to the highest tested dose of 1000 mg/kg bw/day, which has been indicated as the NOAEL for both repeated dose toxicity and reproductive/developmental toxicity.

The calculation of DNELs is based on the NOAEL identified and has to be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the no observed effect level has to be corrected as mentioned below.

INHALATION ROUTE - Systemic effects long term exposure

Corrected starting point for the inhalation route for general population: NAEC general population (24h) = 1000 mg/kg bw/1.15 m³/kg bw

[where: NAEC is the modified starting point; 1000 mg/kg bw is the NOAEL for repeated dose/reproductive/developmental toxicity; 1.15 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure]

Thus, the corrected starting point NAEC was estimated to be 870 mg/m³.

Subsequently other assessment factors have been used to derived the DNEL:

- differences in duration of exposure 6, because the starting value resulted from a subacute study

- remaining differences 2.5

- intraspecies differences 10, for general population

DERMAL ROUTE - Systemic effects long term exposure

Based on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral-to-dermal extrapolation, thus NOAEL has been used as starting point, without any further correction.

Subsequently other assessment factors have been used to derived the DNEL:

- differences in duration of exposure 6, because the starting value resulted from a subacute study

- because the NOAEL was recorded in a study conducted on rats, for interspecies differences the allometric scaling of 4 has been used

- remaining differences 2.5

- intraspecies differences 10, for general population

ORAL ROUTE - Systemic effects long term exposure

No default factor should be introduced when performing on the same route, thus NOAEL has been used as starting point, without any further correction.

Subsequently other assessment factors have been used to derived the DNEL:

- differences in duration of exposure 6, because the starting value resulted from a subacute study

- because the NOAEL was recorded in a study conducted on rats, for interspecies differences the allometric scaling of 4 has been used

- remaining differences 2.5

- intraspecies differences 10, for general population