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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.8 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
370.26 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC (human worker) = NOAEL * (1/0.38 m³/kg bw) * 6.7 m³/10 m³* (7/5) * 0.5 = 300*(1/0.38) *6.7/10*7/5 *0.5 = 370.26 (0.38 m³/kg bw: default respiratory volume for the rat corresponding to the daily duration of human exposure. For workers a correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. Since worker are exposed 5 days per week and the rats were exposed 7 days per week a factor 7/5 was included.

No experimental data on absorption via inhalation route was available. Worst case assumption for absorption was: 50 % orally and 100 % by inhalation = 0.5 correction for inhlation)

Thus, the corrected starting point for workers was 370.26 mg/m³/d for inhalation.

AF for dose response relationship:
1
Justification:
good data about curve dose/response
AF for differences in duration of exposure:
2
Justification:
From subchronic study to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NAEC Human worker
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
NAEC Human worker
AF for the quality of the whole database:
1
Justification:
GLP studies compliant with international guideline
AF for remaining uncertainties:
1
Justification:
100% adsorption for inhalative 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:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
other: Corrected NOAEL
Value:
420 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The corrected starting point for the dermal route for workers: = NOEL*(7/5) = 420 mg/kg bw/day.

No correction from oral to dermal absorption was applied.

AF for dose response relationship:
1
Justification:
good data about curve dose/response
AF for differences in duration of exposure:
2
Justification:
From sub-chronic to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
allometric factor rat to man
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Justification:
GLP studies compliant with international guideline
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance under registration belongs to the category of Stilbene Fluorescent Whitening Agents. This substance and all other members of this category do not show acute toxic effects after oral, inhalation, and dermal administration. They are neither irritant to skin nor eyes, nor genotoxic in-vitro and in-vivo, nor sensitizing. Many substances within this category were tested for subchronic toxicity and four of them were tested for chronic toxicity up to two years with no relevant toxic effects.

In the two generation study performed on rat dosed with OB 3a-MSA a NOAEL of 300 was set for parental toxicity (Turk A.P., 2000).

Based on the parental toxicity in the rat two generation study, the NOAEL of 300 mg/Kg bw/day has been considered as representative, for hazard assessment.

The DNELs for inhalation and dermal long-term exposure are derived from the no observed effect level obtained from this oral toxicity study. In general, the calculation of DNEL is based on the observed effect level, which has to be modified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.61 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
260.87 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected starting point for the inhalation route for general population: = NOAEL * (1/1.15 m³/kg bw/day)*0.5 (1.15 m³/kg bw/day: default respiratory volume for the rat corresponding to the daily duration of human exposure.

No data on absorption via inhalation route was available. Worst case assumption for absorption was: 50 % orally and 100 % by inhalation = 0.5 correcting factor for absorbtion via inhalation)

Thus, the corrected starting point for the general population was 130.43 mg/m³ for inhalation. Subsequently other assessment factors are listed, which have to be taken into account for the final DNEL calculation: remaining differences (2.5), intraspecies differences: general population (10), difference in duration of exposure (2). The DNEL for long-term inhalation exposure, systemic effects is therefore considered to be 2.61 mg/m³.

AF for dose response relationship:
1
Justification:
good data about curve dose/response
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
Justification:
NAEC Human worker
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
NAEC Human worker
AF for the quality of the whole database:
1
Justification:
GLP studies compliant with international guideline
AF for remaining uncertainties:
1
Justification:
100% adsorption for inhalative 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:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
other: Corrected NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point for the dermal route for general population: = NOAELoral = 300 mg/kg bw/day (

No correction from oral to dermal absorption was applied.

Following assessment factors are taken into account for the final DNEL calculation of systemic dermal effects: interspecies differences: human-rat (allometric scaling factor of 4), remaining differences (2.5), intraspecies differences: general population (10), difference in duration of exposure (2).

The resulting DNEL for long-term dermal systemic effects of Stilbene Fluorescent Whitening Agents was 1.5 mg/kg bw/d for general population.

AF for dose response relationship:
1
Justification:
good data about curve dose/response
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
4
Justification:
allometric factor rat to man
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
GLP studies compliant with international guideline
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
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:
1.5 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No extrapolation

AF for dose response relationship:
1
Justification:
good data about curve dose/response
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
Justification:
allometric factor rat to man
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
GLP studies compliant with international guideline
AF for remaining uncertainties:
1
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 substance under registration belongs to the category of Stilbene Fluorescent Whitening Agents. This substance and all other members of this category do not show acute toxic effects after oral, inhalation, and dermal administration. They are neither irritant to skin nor eyes, nor genotoxic in-vitro and in-vivo, nor sensitizing. In the 24 month chronic toxicity study in the rat, conducted on the acid form of the dihydroxyethylamino disulphonated derivative, no treatment-related clinical symptoms and no signs of systemic toxicity were observed throughout the study. Many substances within the category were tested for subchronic toxicity and four of them were tested for chronic toxicity up to two years with no relevant toxic effects.

 

In the two generation study performed on rat dosed with OB 3a-MSA a NOAEL of 300 was set for parental toxicity.

Based on the parental toxicity in the rat two generation study, the NOAEL of 300 mg/Kg bw/day has been considered as representative, for hazard assessment.

  

The DNELs for inhalation and dermal long-term exposure are derived from the no observed effect level obtained from this oral toxicity study with this substance.

In general, the calculation of DNEL is based on the observed effect level, which has to be modified.