Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.35 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Identification of relevant dose descriptor

For the derivation of the DNELs, the key 28-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 100 mg/kg/day.

 

Calculation of DNELs

Systemic, long-term, dermal:

DNEL = NOAEL (oral) / Sum of assessment factors applicable

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since the test article has a molecular weight of > 500 and the log POW is not within -1 to 4, a skin penetration of 10% can be assumed and an assessment factor of 0.1 is applied (ECHA GD chapter R7c). The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4. Intraspecies differences account for a factor of 5. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 6 is employed. Overall, an assessment factor of 30 was employed for the dermal route:

100 mg/kg body weight / 30 = 3.33 mg/kg body weight

 

Systemic, long-term, inhalative

Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) is converted into a NOAEL(corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

Workers: NOAEL (oral) = 100 mg/kg body weight => NOAEL (corrected) = 176.3 mg/m3

DNEL = NOAEL (corrected) / Sum of assessment factors applicable

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: Intraspecies differences account for a factor of 5. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 2 is employed. Overall, an assessment factor of 25 was employed for the inhalation route:

167.3 mg/m3/ 75 = 2.35 mg/m3

 

Systemic, short-term, dermal and inhalative

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated.

 

Local, long-term and short-term, dermal

The substance requires classification for skin sensitization. A reliable DNEL for skin sensitization could not be derived. The qualitative assessment revealed the test substance to be a moderate sensitizer according to the Potency categorization suggested in ECHA guidance document R.8. Personal protective equipment is required to avoid any exposure to skin.

 

Local, long-term and short-term, inhalative

No DNEL for local effects after inhalation was calculated because the substance is not irritating to skin and eyes. The only local effect is skin sensitization, but no quantitative assessment is possible for this effect and therefore no DNEL was derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Identification of relevant dose descriptor

For the derivation of the DNELs, the key 28-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 100 mg/kg/day.

 

Calculation of DNELs

Systemic, long-term, dermal:

DNEL = NOAEL (oral) / Sum of assessment factors applicable

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since the test article has a molecular weight of > 500 and the log POWis not within -1 to 4, a skin penetration of 10% can be assumed and an assessment factor of 0.1 is applied (ECHA GD chapter R7c). The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4. Intraspecies differences account for a factor of 10. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 6 is employed. Overall, an assessment factor of 60 was employed for the dermal route:

100 mg/kg body weight / 60 = 1.67 mg/kg body weight

 

Systemic, long-term, inhalative

Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) is converted into a NOAEL(corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

Workers: NOAEL (oral) = 100 mg/kg body weight => NOAEL (corrected) = 87 mg/m3

DNEL = NOAEL (corrected) / Sum of assessment factors applicable

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: Intraspecies differences account for a factor of 10. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 2 is employed. Overall, an assessment factor of 25 was employed for the inhalation route:

87 mg/m3/ 150 = 0.58 mg/m3

Systemic, long-term, oral:

DNEL = NOAEL (oral) / Sum of assessment factors applicable

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4. Intraspecies differences account for a factor of 10. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 6 is employed. Overall, an assessment factor of 600 was employed for the dermal route:

100 mg/kg body weight / 600 = 0.17 mg/kg body weight

Systemic, short-term, dermal, oral and inhalative

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated.

 

Local, long-term and short-term, dermal

The substance requires classification for skin sensitization. A reliable DNEL for skin sensitization could not be derived since no EC3 value could be determined in the available LLNA. The chemical itself is not handled by the general population. The substance is a dye present in paper articles at low concentrations (< 0.6%) and migration/leaching out of paper articles is very low due to various fixatives within the paper. Therefore, the handling/use of the various finished paper products by the general population is not expected to cause any risks regarding the sensitizing properties of the raw material.

Local, long-term and short-term, inhalative

No DNEL for local effects after inhalation was calculated because the substance is not irritating to skin and eyes. The only local effect is skin sensitization, but no quantitative assessment is possible for this effect and therefore no DNEL was derived. The chemical is not handled by the general population, it is present as a dye at low concentration in finished paper articles and migration/leaching is very low. Therefore, the handling/use of the various finished paper products by the general population is not expected to cause any risks regarding the sensitizing properties of the raw material.