6,15-dihydroanthrazine-5,9,14,18-tetrone

Endpoint summary

Description of key information

 Based on the physico-chemical properties and the results of reliable acute and repeated toxicity and metabolome studies, absorption of the test substance is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties of the substance were specifically investigated. Experimental data on physico-chemical properties and toxicity in rats is used for the assessment.

The substance is a blue powder, which is insoluble in water (< 0.005 mg/L) and octanol (< 0.3 mg/L) and has a molecular weight of 442.4 g/mol. Modelling of the molecular diameter with OASIS CATALOGIC v 5.1.1.5TB showed an average maximum diameter of 2.3 nm. (As half of the fragments were unknown to catalogic, the modelling the substance is outside the structural domain of the model.)

Due to its insolubility in water and octanol active or passive transport through biological membranes is unlikely. As the pigment is one conjugated ring structure, it has a rigid, planar shape which is also not favourable for systemic uptake. This is consistent with the very high average molecular diameter.

 

The studies in rat consistently show absence of systemic toxicity at the limit dose of 1000 mg/kg bw. Treatment of rats consistently shows blue coloration of feces which merely indicates gastrointestinal passage of the intact chromophore. Discoloration of organs or urine is not observed. As part of the subacute oral toxicity study in rats, rat plasma was investigated for potential changes in 251 endogenous plasma components (van Ravenzwaay et al 2014). No effects on the endogenous plasma parameters were identified.

One study with intraperitoneal application of a commercial product containing > 80% of the pigment was performed (BASF 1980). Two weeks after dosing no animal had died from the treatment and necropsy showed intraabdominal substance incorporation in liver and slightly coloured fat tissue. As this effect was observed only after bypassing the biological membranes, it supports the hypothesis that the substance is not taken up after ingestion.

 

The molecule consists of two fused anthraquinone systems and textbook knowledge indicates the quinone oxygen as the relevant site for xenobiotic metabolism. This would eventually lead to hydroxygroups that could be conjugated via sulfotransferases or glucuronosyltransferases. Therefore, apart from the poor solubility in octanol, the substance is considered to have no bioaccumulation potential.

 

Skin permeability is expected to be negligible based on the poor solubilities and the rigid structure.

 

Systemic exposure via inhalation is unlikely as the pigment will behave like an inert nuisance dust. In a cytotoxicity test with a rat alveolar macrophage cell line, uptake in to macrophages was observed. The uptake did not result in a burst of hydrogen peroxide, release of LDH or TNFa. A slight increase in glucuronidase release was observed. Therefore, local effects occurring at situations of lung clearing function overload are considered for the DNEL derivation.