Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

372.52 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor starting point:

NOAEC

Value:

4 656.5 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NAEC worker (8h) = (2641 mg/kg bw/0.38 m³/kg bw) * 6.7 m³/ 10 m³ [where: NAEC is the modified starting point; 2641 mg/kg bw is the NOAEL for developmental toxicity / teratogenicity, based on the substance purity; 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

AF for differences in duration of exposure:

1

Justification:

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 factor

AF for the quality of the whole database:

1

Justification:

Good quality and reliability

AF for remaining uncertainties:

1

Justification:

Good quality and reliability

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:

52.82 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

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:

2 641 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Long-term DNEL for dermal route calculation (systemic effects, route to-route extrapolation) = 2641 mg/kg bw is the NOAEL for repeated dose toxicity oral route / 50 =  52.82 mg/kg bw;

AF workers = 4 (rat to human)*5 (workers)*1(chronic) * 2.5 = 50

AF for dose response relationship:

1

Justification:

data well supported

AF for differences in duration of exposure:

1

Justification:

chronic

AF for interspecies differences (allometric scaling):

4

Justification:

From rat to humans

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:

Good quality and reliability

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

The Derived No Effect Levels for inhalation and dermal long-term exposure are estimated from the No Observed Effect Level obtained from the reproductive toxicity assessment. In general, the calculations of DNELs is based on the observed effect level and have 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.  

SYSTEMIC EFFECTS LONG TERM EXPOSURE - INHALATION ROUTE  NAEC worker (8h) = (2641 mg/kg bw/0.38 m³/kg bw) * 6.7 m³/ 10 m³ [where: NAEC is the modified starting point; 2641 mg/kg bw is the NOAEL for repeated dose toxicity (oral route); 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/kg for light activity)].

Thus, the corrected starting point NOAEC was estimated to be 4656.50 mg/m³.

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

- differences in duration of exposure 1, because the starting value resulted from a chronic study

- remaining differences 2.5

- intraspecies differences 5, for worker population  

The overall assessment factor (AF) is equal to: 1* 2.5 * 5 = 12.5

DNEL is therefore obtained as followed: DNEL = NAEC / AF (overall assessment factor) = 4656 mg/ m3 / 12.5 = 372.52 mg/m3  

 

SYSTEMIC EFFECTS LONG TERM EXPOSURE - DERMAL ROUTE  

The following assessment factors have been used to derived the DNEL:

- differences in duration of exposure 1, because the starting value resulted from a chronic study

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

- remaining differences 2.5

- intraspecies differences 5, for worker population.  

The overall assessment factor (AF) is equal to: 1 * 4* 2.5 * 5 = 50  

DNEL is therefore obtained as followed:  

DNEL = NOAEL / AF (overall assessment factor) = 2641 mg/kg bw/day / 50 = 52.82 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

91.86 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

2 296.52 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEC= NOAEL/1.15 (sRV for 24h rat)

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

1

Justification:

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:

Good quality and reliability

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:

26.41 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

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:

2 641 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL = 2641/ 100 (AF) = 26.41

AF workers = 4 (rat to human)*10 (general population)*1(chronic) * 2.5 = 100

AF for dose response relationship:

1

Justification:

data well suported

AF for differences in duration of exposure:

1

Justification:

chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

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:

Good quality and reliability

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

DNEL related information

Explanation for the modification of the dose descriptor starting point:

This substance is not classified for acute toxicity hazards for this reason no acute DNEL(S) need to be calculate.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

26.41 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

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:

2 641 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL = 2641/ 100 (AF) = 26.41.

AF workers = 4 (rat to human)*10 (general population)*1(chronic) * 2.5 = 100

AF for dose response relationship:

1

Justification:

Data well supported

AF for differences in duration of exposure:

1

Justification:

chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

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:

Good quality and reliability

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

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 Levels for oral, inhalation and dermal long-term exposure are estimated from the No Observed Effect Level obtained from the reproductive / developmental toxicity assessment.

In general, the calculations of DNELs is based on the observed effect level and have 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.    

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - INHALATION ROUTE  

NOAEC general population = (NOAEL oral-rat / sRV rat general population)

NOAEL oral – rat = 2641 mg/kg bw

sRV (standard respiratory volume) general population: rat 24 h exposure (m3/kb bw) = 1.15

Thus, the corrected starting point NOAEC was estimated to be 2296.52 mg/m³.

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

- differences in duration of exposure 1, because the starting value resulted from a chronic study

- for interspecies differences the allometric scaling of 1 since the differences were evelauated in the NOAEC calculation.

- remaining differences 2.5

- intraspecies differences 10, for general population  

The overall assessment factor (AF) is equal to: 1 * 1 * 2.5 * 10 = 25

DNEL is therefore obtained as followed: DNEL = NOAEC / AF (overall assessment factor) = 91.86 mg/m3    

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - DERMAL ROUTE  

The following assessment factors have been used to derived the DNEL:

- differences in duration of exposure 1, because the starting value resulted from a chronic study

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

- remaining differences 2.5

- intraspecies differences 10, for general population.  

The overall assessment factor (AF) is equal to: 1 * 4* 2.5 * 10 = 100    

DNEL is therefore obtained as followed:  DNEL = NOAEL / AF (overall assessment factor) = 2641 mg/kg bw/day / 100 = 26.41 mg/kg bw/day

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - ORAL ROUTE

The following assessment factors have been used to derived the DNEL:

- differences in duration of exposure 1, because the starting value resulted from a chronic study

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

- remaining differences 2.5

- intraspecies differences 10, for general population.  

The overall assessment factor (AF) is equal to: 1 * 4* 2.5 * 10 = 100  

DNEL is therefore obtained as followed:  

DNEL = NOAEL / AF (overall assessment factor) = 2641 mg/kg bw/day / 100 = 26.41 mg/kg bw/day