Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.167 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
Modified dose descriptor starting point:
NOAEC
Value:
87.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 0.4 m³/kg bw. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest was considered to be 6.7 m³/10 m³. Therefore, the modified dose descriptor starting point is 87.5 mg/m³ (= 100 / 2 / 0.4 x (7/10)).

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for other interspecies differences:
2.5
Justification:
Remaining difference
AF for intraspecies differences:
5
Justification:
Worker population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore, the modified dose descriptor starting point is 2500 mg/kg bw/day

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for other interspecies differences:
2.5
Justification:
Remaining difference
AF for intraspecies differences:
5
Justification:
Worker population
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

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 


Short-term toxicity: According to the REACH guideline (R8, Appendix R 8-8), 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 risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure. The substance is also not classified as irritating or sensitizing to the skin and therefore no derivation of the DNEL for local dermal effects needs to be derived. No data is available whether the test substance could cause irritation to the respiratory tract and therefore no DNEL could be derived.


Long-term toxicity: A subacute (28-days) oral toxicity study is available in rats. Haemolytic anaemia was observed in both genders at 300 and 1000 mg/kg/d. Microscopically, this was evident by extramedullary haematopoiesis in bone marrow and spleen. This also correlated with dose-dependently lower levels of red blood cell parameters (RBC, Hb and Hct) and a concurrent increase in reticulocytes and mean cell haemoglobin and mean cell volume. Whereas the effects were moderate at 1000 mg/kg/d, only a slight anaemia was found at 300 mg/kg/d. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. The low log Pow (1.98) value suggests that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 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
Modified dose descriptor starting point:
NOAEC
Value:
43.48 mg/m³
Explanation for the modification of the dose descriptor starting point:

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 1.15 m³/kg bw. Therefore the modified dose descriptor starting point is 43.48 m³/kg bw (= 100 / 2 / 1.15)

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-acute toxicity study
AF for intraspecies differences:
10
Justification:
Defult assesment factor for consumers
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 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
Modified 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 exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore the modified dose descriptor starting point is 25000 mg/kg bw/day

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for other interspecies differences:
2.5
Justification:
Remaining differences.
AF for intraspecies differences:
10
Justification:
Default assessment for consumers.
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:
0.167 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
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required as it is oral route.

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
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

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 


Short-term toxicity: According to the REACH guideline (R8, Appendix R 8-8), 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 risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure. The substance is also not classified as irritating or sensitizing to the skin and therefore no derivation of the DNEL for local dermal effects needs to be derived. No data is available whether the test substance could cause irritation to the respiratory tract and therefore no DNEL could be derived.


Long-term toxicity: A subacute (28-days) oral toxicity study is available in rats. Haemolytic anaemia was observed in both genders at 300 and 1000 mg/kg/d. Microscopically, this was evident by extramedullary haematopoiesis in bone marrow and spleen. This also correlated with dose-dependently lower levels of red blood cell parameters (RBC, Hb and Hct) and a concurrent increase in reticulocytes and mean cell haemoglobin and mean cell volume. Whereas the effects were moderate at 1000 mg/kg/d, only a slight anaemia was found at 300 mg/kg/d. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route.


According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. The low log Pow (1.98) value suggests that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation.