Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

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:
45 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
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 >1710 mg/kg bw; LC50 inhalation > 4.25 mg/L) and no hazards leading to classification and labeling were identified. It is considered unlikely that the Diarylide Yellow 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 Diarylide Yellow 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 diarylide yellow 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.But, as a worst case consideration a DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-toute extrapolation of the data after long-term oral exposure. In a chronic toxicity study with Pigment Yellow 12 a NOAEL of 555 mg/kg bw/d (male rats) has been derived (Laboratorium für Pharmakologie und Toxikologie, 1977a; Leuschner, 1978).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 Diarylide Yellow Pigments are not likely to become systemically available in relevant amounts and based on ECETOC (2010).No time extrapolation factor is necessary, because a chronic toxicity study is available. This results in an overall assessment factor of 12 (3 x 4). Based on these data a DNEL long term dermal exposure - systemic effects of 45 mg/kg bw/d is derived for Diarylide Yellow Pigments of this catagory.

Long-term inhalation exposure - systemic effects

There are no studies with long term inhalation exposure to Diarylide Yellow Pigments of this category available. Two subacute inhalation studies with Pigment Yellow 13 in rats (CIBA, 1979e, f) reveal that the test item does not exert systemic effects but induces local effects due to the deposition of the test material in the respiratory tract.The substances of this category are not likely to be systemically available after inhalation. Therefore no DNEL ¿long-term inhalation exposure ¿ systemic effects¿ is derived.

Long-term dermal exposure - local effects

A DNEL is not derived because Diarylide Yellow 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

Diarylide Yellow Pigments do not cause irritation, corrosion or sensitization and no studies have been located which investigate the long term inhalation toxicity of Diarylide Yellow Pigments of this category. But two studies investigating subacute inhalative toxicity of Pigment Yellow 13 in rats are available, which reveal that the test item does not exert systemic effects but induces local effects due to the deposition of the test material in the respiratory tract (CIBA, 1979e, f): In a 21-day inhalation study (6 h/d, 5 d/w) with Pigment Yellow 13 in rats only minimal deposition of the test material in the respiratory tract without inflammatory response are observed at the lowest test concentration (52 mg/m3). These effects are considered not to be adverse, i. e. 52 mg/m3is a NOAEC. At higher test concentrations substance deposition along with inflammatory responses up to pneumoconiosis are observed. These effects are typical for inert dusts. 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:
28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
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:
28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
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 > 1710 mg/kg bw; LC50 inhalation > 4.25 mg/L) and no hazards leading to classification and labeling were identified. It is considered unlikely that the Diarylide Yellow 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 Diarylide Yellow 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, Diarylide Yello Pigments of this category are considered to behave like inert dusts.

Long-term dermal exposure - systemic effects

No data on toxicity of Diarylide Yellow 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 chronic toxicity study with Pigment Yellow 12 a NOAEL of 555 mg/kg bw/d (male rats) has been derived (Laboratorium für Pharmakologie und Toxikologie, 1977a; Leuschner, 1978). 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 Diarylide Yellow Pigments are not likely to become systemically available in relevant amounts and based on ECETOC (2010).No time extrapolation factor is necessary, because a chronic toxicity study is available.The resulting overall assessment factor is 20 (5 x 4). Based on these data a general population DNEL "long-term dermal exposure - systemic effects" of 28 mg/kg bw/day is derived for Diarylide Yellow Pigments of this category.

Long-term inhalation exposure - systemic effects

No data on toxicity of Diarylide Yellow Pigments of this category after long-term inhalation exposure are available.Two subacute inhalation studies with Pigment Yellow 13 in rats (CIBA, 1979e, f) reveal that the test item does not exert systemic effects but induces local effects due to the deposition of the test material in the respiratory tract. 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

Information on chronic toxicity of diarylide yellow pigments of this categroy are available from carcinogenicity studies performed with Pigment Yellow 12 and Pigment Yellow 83 in rats and mice. Pigment Yellow 83 were fed in concentrations up to 9000 ppm to rats and mice. No substance related toxicity were observed in any study, resulting in a NOAEL for rats of about 600 mg/kg bw/d and for mice of about 2000 mg/kg bw/d (Leuschner, 1978; Laboratorium für Pharmakologie und Toxikologie, 1976b, 1977a, b, 1980b). Carcinogenicity studies with Pigment Yellow 12 were performed in rats and mice which received either up to 5% test item in the diet (NCI, 1978) or up to 9000 ppm in the diet (Leuschner, 1978; Laboratorium für Pharmakologie und Toxikologie, 1976a, 1980a). No adverse effects were observed in any study with mice (Leuschner, 1978; Laboratorium für Pharmakologie und Toxikologie, 1976a; NCI, 1978). The only observed adverse effect in one of the rat-studies was an increased incidence of basophilic cytoplasm in hepatocytes of treated rats (2.5% or 5% P. Y. 12 in diet; NCI, 1978). The LOAEL in this study was 2.5% P. Y. 12 in diet (corresponding to about 1000 and 1250 mg/kg bw/d in males and females, respectively). In the other carcinogenicity study with rats (Leuschner, 1978; Laboratorium für Pharmakologie und Toxikologie, 1980a) no adverse effects occurred up to the highest concentration tested (9000 ppm P. Y. 12 in diet corresponding to 555 and 579 mg/kg bw/d in males and females, respectively). These findings are supported by several other subacute and subchronic toxicity studies with different Diarylide Yellow Pigments. Based on the carcinogenicity studies rats were regarded to be the most sensitive species towards chronic oral toxicity of Pigment Yellow and a NOAEL of 555 mg/kg bw/d in male rats was selected as starting point for the derivation of the DNEL ¿long-term oral exposure - systemic effects¿.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 Diarylide Yellow Pigments are not likely to become systemically available in relevant amounts and based on ECETOC (2010).No time extrapolation factor is necessary, because a chronic toxicity study is available.The resulting overall assessment factor is 20 (5 x 4).This results in an overall assessment factor of 20 (5 x 4). Based on these data a DNEL long term oral exposure - systemic effects of 28 mg/kg bw/d is derived for diarylide yellow pigments of this catagory.

Long-term dermal exposure - local effects

A DNEL is not derived because Diarylide Yellow 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

No studies were located which investigated the long term inhalation toxicity of Diarylide Yellow Pigments of this category, but two studies investigating subacute inhalative toxicity of Pigment Yellow 13 in rats were available, which revealed that the test item did not exert systemic effects but induced local effects due to the deposition of the test material in the respiratory tract (CIBA, 1979e, f): In a 21-day inhalation study (6 h/d, 5 d/w) with P. Y. 13 in rats only minimal deposition of the test material in the respiratory tract without inflammatory response are observed at the lowest test concentration (52 mg/m3). These effects are considered not to be adverse, i. e. 52 mg/m3is a NOAEC. At higher test concentrations substance deposition along with inflammatory responses up to pneumoconiosis are observed. These effects are typical for inert dusts. No DNEL "long-term inhalation exposure - local effects" is derived for the substances of this category, becausethe use and exposure pattern "long-term inhalation" exposure is not considered relevant for the general population