Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
147 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
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:
42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Acute / short-term dermal exposure - systemic effects

Acute / short-term inhalation exposure - systemic effects

Worker DNELs for acute exposure - systemic effects are not derived, because no relevant acute toxicity was observed (LD50 oral >2000 mg/kg bw; LD50 dermal >2000 mg/kg bw; LC50 inhalation > 3.1 mg/L) and no hazards leading to classification and labeling were identified. It is considered unlikely that the quinacridone pigments of this category become systemically bioavailable after dermal or inhalation exposure. Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing.

Acute / short term dermal exposure - local effects

Acute / short term inhalation exposure - local effects

Worker DNELs for acute exposure - local effects are not derived, because quinacridone pigments of this category have not to be classified as irritating to skin or eyes, are considered unlikely to become bioavailable in the skin and are considered not to be classified regarding respiratory tract irritation. Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing. Apart from that, relevant occupational exposure limits for inert dusts should be applied (see below for justification).

Long-term dermal exposure - systemic effects

No data on toxicity of Quinacridone Pigments of this category after long-term dermal exposure are available. The substances of this category are not likely to be systemically available after dermal exposure. As worst case consideration a DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-route extrapolation of the data after long-term oral exposure: In a subchronic oral study with rats which received Pigment Red 122 (2006) a NOAEL of 1000 mg/kg bw/d has been derived. This NOAEL is regarded as starting point for the derivation of the worker DNEL "long-term dermal exposure - systemic effects". Based on the very low water and octanol solubility it is assumed that the dermal absorption and the oral absorption are very small and that absorption is similar for both routes of exposure and between species. In the absence of any substance specific data a default factor of 3 is used for intraspecies extrapolation based on ECETOC (2010) (Technical Report ‘Guidance on Assessment Factors to Derive DNELs’, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Brussels, Belgium, 2010). An allometric scaling factor of 4 is applied to account for constitutionally species differences. A factor 1 was applied for remaining interspecies differences, because Quinacridone Pigments are not likely to become systemically available in relevant in relevant amounts and based on ECETOC (2010) While there are no indications for substance accumulation in the body or for an increase of toxicity with increasing exposure duration, a factor of 2 is used for time extrapolation. The resulting overall assessment factor is 24 (3 x 4 x 2). Based on these data a worker DNEL "long-term dermal exposure - systemic effects" of 42 mg/kg bw/day is derived for Quinacridone Pigments of this category.

Long-term inhalation exposure - systemic effects

No data on toxicity of Quinacridone Pigments of this category after long-term inhalation exposure are available. The substances of this category are not likely to be systemically available after inhalation. As worst case consideration a worker DNEL "long-term inhalation exposure -systemic effects" can be derived by route-to-route extrapolation of the data after long-term oral exposure: In a subchronic oral study with rats which received Pigment Red 122 (2006) a NOAEL of 1000 mg/kg bw/d has been derived. This NOAEL is regarded as starting point for the derivation of the worker DNEL "long-term inhalation exposure -systemic effects". Based on the very low water and octanol solubility it is assumed that the oral absorption and the inhalation absorption are very small and that absorption is similar for both routes of exposure and between species. Nevertheless, the default factor of 2 for oral-to-inhalation extrapolation will be applied. The corrected inhalatory NOAEC is obtained according to the procedure described in the Guidance on information requirements and chemical safety assessment R.8 (corrected inhalatory NOAEC = oral NOAEL x 1/0.38 m³/kg/day x 6.7 m³/10 m³; with RVrat-8h 0.38 m³/kg/day; sRVhuman 6.7 m³/person; wRV 10 m³/person) as 1763 mg/m³. In the absence of any substance specific data a default factor of 3 for intraspecies extrapolation based on ECETOC (2010) (Technical Report ‘Guidance on Assessment Factors to Derive DNELs’, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Brussels, Belgium, 2010), and a default oral-to-inhalation factor of 2 are used. A factor 1 was applied for remaining interspecies differences, because Quinacridone Pigments are not likely to become systemically available in relevant in relevant amounts and based on ECETOC (2010). Although there are no indications for substance accumulation in the body or for an increase of toxicity with increasing exposure duration after oral exposure, a steady state from repeated inhalation exposure may require longer time; therefore the default factor of 2 is used for time extrapolation. The resulting overall assessment factor is 12 (3 x 2 x 2). Based on these data a DNEL "long-term inhalation exposure -systemic effects" of 147 mg/m³ would be derived (cf. local effects).

Long-term dermal exposure - local effects

A DNEL is not derived because quinacridone pigments do not cause irritation, corrosion and/or sensitization and no data for setting a worker DNEL "long-term dermal exposure -local effects" are available.

Long-term inhalation exposure - local effects

Quinacridone Pigments do not cause irritation, corrosion or sensitization and no data for setting a worker DNEL "long-term inhalation exposure -local effects" are available. Based on the physico-chemical properties and the results of toxicity testing it can reasonably be assumed that Quinacridone Pigments, when aerosolized in respirable form, will behave like an inert dust. Inert dusts can exert local effects in the lung and, therefore, general dust limits of 10 mg/m³ for the inhalable airborne fraction and 3 mg/m³ for the respirable airborne fraction are used in setting occupational exposure limits in many countries. For this reason, the DNEL is set to the general dust limit which is considered protective of local effects from long-term inhalation exposure.

General Population - Hazard via inhalation route

Systemic effects

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:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
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:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Acute / short-term dermal exposure - systemic effects

Acute / short-term inhalation exposure - systemic effects

Acute / short-term oral exposure - systemic effects

General population DNELs for acute exposure - systemic effects are not derived, because no relevant acute toxicity was observed (LD50 oral > 2000 mg/kg bw; LD50 dermal > 2000 mg/kg bw; LC50 inhalation >3.1 mg/L) and no hazards leading to classification and labeling were identified. It is considered unlikely that the quinacridone pigments of this category become systemically bioavailable after oral, dermal or inhalation exposure. Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing.

Acute / short term dermal exposure - local effects

Acute / short term inhalation exposure - local effects

General population DNELs for acute exposure - local effects are not derived, because quinacridone pigments of this category have not to be classified as irritating to skin or eyes, are considered unlikely to become bioavailable in the skin and are considered not to have to be classified regarding respiratory tract irritation. Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing. When aerosolized in respirable form, quinacridone pigments of this category are considered to behave like inert dusts.

Long-term dermal exposure - systemic effects

No data on toxicity of Quinacridone Pigments of this category after long-term dermal exposure are available. The substances of this category are not likely to be systemically available after dermal exposure. As worst case consideration a general population DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-route extrapolation of the data after long-term oral exposure: In a subchronic oral study with rats which received Pigment Red 122 (Anon., 2006) a NOAEL of 1000 mg/kg bw/d has been derived. This NOAEL is regarded as starting point for the derivation of the general population DNEL "long-term dermal exposure - systemic effects". Based on the very low water and octanol solubility it is assumed that the dermal absorption and the oral absorption are very small and that absorption is similar for both routes of exposure and between species. In the absence of any substance specific data a default factor of 5 is used for intraspecies extrapolation based on ECETOC (2010) (Technical Report ‘Guidance on Assessment Factors to Derive DNELs’, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Brussels, Belgium, 2010). An allometric scaling factor of 4 is applied to account for constitutionally species differences. A factor 1 was applied for remaining interspecies differences, because Quinacridone Pigments are not likely to become systemically available in relevant in relevant amounts and based on ECETOC (2010). While there are no indications for substance accumulation in the body or for an increase of toxicity with increasing exposure duration, a factor of 2 is used for time extrapolation. The resulting overall assessment factor is 40 (5 x 4 x 2). Based on these data a general population DNEL "long-term dermal exposure - systemic effects" of 25 mg/kg bw/day is derived for Quinacridone Pigments of this category.

Long-term inhalation exposure - systemic effects

No data on toxicity of quinacridone pigments of this category after long-term inhalation exposure are available. The substances of this category are not likely to be systemically available after inhalation. Moreover, the use and exposure pattern ¿long-term inhalation¿ is not considered relevant for the general population. Therefore, no general population DNEL "long-term inhalation exposure - systemic effects" is derived.

Long-term oral exposure - systemic effects

Toxicity of Quinacridone Pigments of this category after repeated oral exposure has been investigated in several studies. No substance related toxicity was observed in a guideline 28-day oral toxicity study in rats with Pigment Red 282 (NOAEL 1000 mg/kg bw/d; Damme et al., 2005) and in a guideline 90-day oral toxicity study in rats with Pigment Red 122 (NOAEL 1000 mg/kg bw/d; Anon., 2006). These findings are supported by several subacute pre-guideline studies for Pigment Violet 19 and Pigment Red 209. The NOAEL observed in the 90-day oral toxicity study is selected as starting point for the derivation of the general population DNEL "long-term oral exposure - systemic effects". Based on the very low water and octanol solubility it is assumed that the oral absorption is very small and that absorption is similar between species. In the absence of any substance specific data a default factor of 5 is used for intraspecies extrapolation based on ECETOC (2010) (Technical Report ‘Guidance on Assessment Factors to Derive DNELs’, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Brussels, Belgium, 2010). An allometric scaling factor of 4 is applied to account for constitutionally species differences. A factor 1 was applied for remaining interspecies differences, because Quinacridone Pigments are not likely to become systemically available in relevant in relevant amounts and based on ECETOC (2010). While there are no indications for substance accumulation in the body or for an increase of toxicity with increasing exposure duration, a factor of 2 is used for time extrapolation. The resulting overall assessment factor is 40 (5 x 4 x 2). Based on these data a general population DNEL "long-term oral exposure - systemic effects" of 25 mg/kg bw/day is derived for Quinacridone Pigments of this category.

Long-term dermal exposure - local effects

A DNEL is not derived because quinacridone pigments do not cause irritation, corrosion and/or sensitization and no data for setting a general population DNEL "long-term dermal exposure -local effects" are available.

Long-term inhalation exposure - local effects

A DNEL is not derived because quinacridone pigments do not cause irritation, corrosion and/or sensitization and no data for setting a general population DNEL "long-term inhalation exposure -local effects" are available. Moreover, the use and exposure pattern "long-term inhalation" exposure is not considered relevant for the general population.