Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
58.8 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):
30
Modified dose descriptor starting point:
NOAEC
Value:
1 763.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC corr = (NOAEL oral/vSRrat) X (vSR human / vWSRhuman) = (1000/0.38) x (6.7/10)
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable (accounted for by respiratory volumes)
AF for other interspecies differences:
1
Justification:
Covered by allometric scaling
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Good quality database
AF for remaining uncertainties:
1
Justification:
None
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:
16.67 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):
120
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
[(NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration) -response for human health’); where: NOAELoral rat = 1000 mg/kg bw/day; ABSoral-rat = 100%; ABSderm-rat = ABSderm-human = 50%).
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
Covered by allometric scaling
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Good quality database
AF for remaining uncertainties:
1
Justification:
None
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Repeated dose toxicity/systemic effects:

Base for deriving systemic long-term DNELs is a 28 day oral toxicity study in rats. Local effects in the stomach suggest a local NOAEL of 62.5 mg/kg body weight/day (cellular infiltrations which can be attributed to irritating properties of the test substance). This was not associated with destructive processes and reversible. At the dose level of 62.5 mg/kg body weight/day incidence and severity of the inflammatory reaction in the glandular stomach was comparable to the control group. As these local effects were the only adverse effects seen in the repeat-dose study, the systemic NOAEL was considered to be 1000 mg/kg body weight/day which was used to derive systemic DNELs using ECHA Guidance values for assessment factors (based on clinical signs, body weight changes, food consumption, hematologic parameters, clinical chemistry, urinalysis, organ weights, gross pathology).

There is no data available that would indicate a specific concern for the inhalation and dermal route. Thus, route-to-route extrapolation is justified.

 

Acute toxicity/local effects:

According to ECHA guidance there is no established accepted methodology to derive no-effect-levels for acute toxicity. It is considered not only cumbersome and resource-intensive but probably unnecessary, as the long-term DNEL is normally sufficient to ensure that effects do not occur. It is proposed that a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. The test item is not classified for acute toxicity based on a LD50> 2000 mg/kg/d for the oral and dermal route.

Data on skin irritation/corrosion and eye irritation in vivo suggest a low hazard potential with regards to local effects.

Overall, a low hazard potential is concluded for the test item.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.4 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):
60
Modified dose descriptor starting point:
NOAEC
Value:
1 763.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC corr = (NOAEL oral/vSRrat) X (vSR human / vWSRhuman) = (1000/0.38) x (6.7/10)
AF for dose response relationship:
1
Justification:
Starting point is a NOEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable (accounted for by respiratory volumes)
AF for other interspecies differences:
1
Justification:
Covered by allometric scaling
AF for intraspecies differences:
10
Justification:
Consumers
AF for the quality of the whole database:
1
Justification:
Good quality database
AF for remaining uncertainties:
1
Justification:
None
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:
8.33 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):
240
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
[(NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration) -response for human health’); where: NOELoral rat = 1000 mg/kg bw/day; ABSoral-rat = 100%; ABSderm-rat = ABSderm-human = 50%).
AF for dose response relationship:
1
Justification:
Starting point is a NOEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
Covered by allometric scaling
AF for intraspecies differences:
10
Justification:
Consumers
AF for the quality of the whole database:
1
Justification:
Good quality database
AF for remaining uncertainties:
1
Justification:
None
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
Covered by allometric scaling
AF for intraspecies differences:
10
Justification:
Consumers
AF for the quality of the whole database:
1
Justification:
Good quality database
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Repeated dose toxicity/systemic effects:

Base for deriving systemic long-term DNELs is a 28 day oral toxicity study in rats. Local effects in the stomach suggest a local NOAEL of 62.5 mg/kg body weight/day (cellular infiltrations which can be attributed to irritating properties of the test substance). This was not associated with destructive processes and reversible. At the dose level of 62.5 mg/kg body weight/day incidence and severity of the inflammatory reaction in the glandular stomach was comparable to the control group. As these local effects were the only adverse effects seen in the repeat-dose study, the systemic NOAEL was considered to be 1000 mg/kg body weight/day which was used to derive systemic DNELs using ECHA Guidance values for assessment factors (based on clinical signs, body weight changes, food consumption, hematologic parameters, clinical chemistry, urinalysis, organ weights, gross pathology).

There is no data available that would indicate a specific concern for the inhalation and dermal route. Thus, route-to-route extrapolation is justified.

 

Acute toxicity/local effects:

According to ECHA guidance there is no established accepted methodology to derive no-effect-levels for acute toxicity. It is considered not only cumbersome and resource-intensive but probably unnecessary, as the long-term DNEL is normally sufficient to ensure that effects do not occur. It is proposed that a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. The test item is not classified for acute toxicity based on a LD50> 2000 mg/kg/d for the oral and dermal route.

Data on skin irritation/corrosion and eye irritation in vivo suggest a low hazard potential with regards to local effects.

Overall, a low hazard potential is concluded for the test item.

For consumer use, it should be noted that due to the chemical reaction of the dye with the fabric during the dyeing process, the test substance is covalently bound to the textile. It is therefore unlikely that the consumer is exposed to the dye from contact to the dyed textile. For home-dyeing, consumer use is restricted to dyeing with the washing machine (closed system). The preparation provided for home-dyeing is designed in a way that exposure of the consumer to the powder can be excluded. A consumer exposure to the test substance can therefore be omitted.