Registration Dossier

Administrative data

Description of key information

Repeated oral toxicity:
The toxicity of Pigment Red 112 when given by oral administration (gavage) to groups of 5 rats per sex per dose for 28 consecutive days at dosages of 0, 100, 300 or 1000 mg/kg bw/day, for 7 days/week have been investigated. No toxicologically significant changes were noted in any of the parameters investigated in this study (i.e. clinical appearance, functional observations, body weight, food consumption, clinical laboratory investigations, macroscopic examination, organ weights, and microscopic examination). Red staining of various body parts, red faeces and reddish contents of the gastro-intestinal tract noted among all groups treated with the test substance was considered to be related to staining properties of the test substance, and not to represent signs of systemic toxicity. No correlating histopathological abnormalities were noted. On the basis of these results, the high dose level of 1000 mg/kg/day was considered to be the No-Observed-Adverse-Effect Level (NOAEL) for Pigment Red 112.
Repeated dermal toxicicty:
The dermal route was waived; substance is not classified for this endpoint. The substance is considered not to exert any local or systemic adverse effects.
Repeated inhalation toxicicty:
The inhalation route was waived; substance is not classified for this endpoint. When aerosolized in respirable form; when aerosolized in respirable form, the substance is considered likely to behave like an inert dust.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Justification for classification or non-classification

Pigment Red 112 does not have to be classified regarding systemic and target organ toxicity after repeated oral exposure according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC), because

- Pigment Red 112 caused no relevant systemic effects and revealed a NOAEL of 1000 mg/kg/day in a 28 -day oral gavage study in rats and due to the virtual absence of bioavailability and toxic effects of Pigment Red 112, the performing of a 90-day repeated dose toxicity study was considered scientifically unnecessary.

 

It can reasonably be deduced that Pigment Red 112 does not exert systemic toxic effects after repeated dermal application and thus does not have to be classified according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and that testing is not scientifically necessary, because

- Pigment Red 112 caused no relevant systemic effects and revealed a NOAEL of 1000 mg/kg/day in a 28-day oral gavage study in rats and due to the virtual absence of bioavailability and toxic effects of Pigment Red 112, the performing of a 90-day repeated dose toxicity study was considered scientifically unnecessary,

- it is unlikely that Pigment Red 112 becomes systemically bioavailable after skin contact due to its extremely low solubility in water and n-octanol,

- Pigment Red 112 does not have to be classified as skin sensitizing (refering to the pigment as such notwithstanding effects of impurities) or as skin or eye irritating, indicating that its chemical inertness and extremely low solubility in water and n-octanol largely prevent interaction with living cells and tissues.

 

It can reasonably be deduced that Pigment Red 112 does not have to be classified regarding systemic and target organ toxicity after repeated inhalation exposure according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and that testing is not scientifically necessary, because

- Pigment Red 112 caused no relevant systemic effects and revealed a NOAEL of 1000 mg/kg/day in a 28-day oral gavage study in rats;

- due to the virtual absence of bioavailability and toxic effects of Pigment Red 112, performance of a 90-day repeated dose toxicity study was considered scientifically unnecessary,

- it is unlikely that Pigment Red 112 becomes systemically bioavailable to a relevant extend after inhalation due to its extremely low solubility in water and n-octanol,

- Pigment Red 122 does not have to be classified as skin sensitizing (refering to the pigment as such notwithstanding effects of impurities) or

as skin or eye irritating, indicating that its chemical inertness and extremely low solubility in water and n-octanol largely prevent interaction with living cells and tissues,

- and although Pigment Red 112, when aerosolized in respirable form, is likely to behave like an inert dust which may cause a mild form of inflammatory lung reaction upon high long-term, repeated inhalation exposure mediated by the activation of alveolar macrophages by deposited non-biodegradable particles.