Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.65 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
DNEL value:
109.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
Due to particle size distribution, inhalable / respirable particles are negligible. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Hence NOAEL for oral toxicity is considered the appropriate endpoint for hazard assessment. Therefore oral absorption in rat is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. Allometric scaling factor: 4; BW (human) = 70 kg Hrv = Human respiration rate = 10 m3 / person. Therefore, corrected NOAEC (inhalation) = 109.4 mg/m3 (62.5/4 * 70/10)
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
700 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 500 mg/m³
Explanation for the modification of the dose descriptor starting point:
Due to particle size distribution, inhalable / respirable particles are negligible. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Hence NOAEL for oral toxicity is considered the appropriate endpoint for hazard assessment. Therefore oral absorption in rats is assumed to be 100% and inhalation absorption in rats is assumed to be 100%. Guidance on information requirements and chemical safety assessment; Chapter R.7a: Endpoint specific guidance, section R.7.4.5.2 Concluding on suitability for Chemical Safety Assessment for acute toxicity states that when a limit test has been conducted, and no adverse effects on health have been observed, then the limit dose can be regarded as the NOAEL. Allometric scaling factor: 4 BW(human) = 70 kg, Hrv = Human respiration rate = 10 m3 / person. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. = 2000 / 4 * 70/10 = 3500 mg/m3. For workers (in case of 8 hour exposure / day).
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
1.04 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
DNEL value:
125 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume that oral absorption in rat is 100% and dermal absorption in humans is 50% as worst case.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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

The test substance does not have any local irritating or sensitizing effects in animals. There are no inhalation data available for the substance. By extrapolation it is possible to calculate systemic DNELS for short term and some long term exposure; however calculation of local DNELS on the basis of the available data does not seem to be reasonable, as the substance is not classified for toxicological effects.

Given that exposure considerations for skin and eye exposure in the dyeing industry where the substance is used can be stated as negligible and prevented, it is therefore the consideration of the registrant that quantitative local effects based on animal data cannot be conducted. Instead, qualitative assessments of acute/short term and long term effects have instead been conducted, based on the data available. By extrapolation it is possible to calculate systemic DNELS for short term and some long term exposure; however calculation of local DNELS for local effects on the basis of the available data does not seem to be reasonable, as the substance is not classified for toxicological effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.91 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
DNEL value:
54.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Due to particle size distribution, inhalable / respirable particles are negligible. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Therefore, 100% oral absorption in rats is assumed and 100% inhalation absorption in humnas is assumed. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. Allometric scaling factor: 4; BW (human) = 70 kg Hrv = Human respiration rate = 20 m3 / person. Therefore, corrected NOAEC (inhalation) = 54.7 mg/m3 (62.5/4 * 70/20)
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor of 10 for general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
350 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 500 mg/m³
Explanation for the modification of the dose descriptor starting point:
Due to particle size distribution, inhalable / respirable particles are negligible. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Hence NOAEL for oral toxicity is considered the appropriate endpoint for hazard assessment. Therefore oral absorption in rats is assumed to be 100% and inhalation absorption in rats is assumed to be 100%. Guidance on information requirements and chemical safety assessment; Chapter R.7a: Endpoint specific guidance, section R.7.4.5.2 Concluding on suitability for Chemical Safety Assessment for acute toxicity states that when a limit test has been conducted, and no adverse effects on health have been observed, then the limit dose can be regarded as the NOAEL. Allometric scaling factor: 4 BW(human) = 70 kg, Hrv = Human respiration rate = 10 m3 / person. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. = 2000 / 4 * 70/10 = 3500 mg/m3.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor of 10 for general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
0.52 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
DNEL value:
125 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume that oral absorption in rat is 100% and dermal absorption in humans is 50% as worst case.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general opoulation is 10
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaning uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for the general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
0.26 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
DNEL value:
62.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for the general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for the general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The test substance is not classified for any local irritating or sensitizing effects in animals. There are no inhalation data available for the substance. By extrapolation it is possible to calculate systemic DNELS for short term and some long term exposure; however calculation of local DNELS on the basis of the available data does not seem to be reasonable, as the substance is not classified for toxicological effects.

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.