Ethanaminium, N-[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthalenyl]methylene]-2,5-cyclohexadien-1-ylidene]-N-ethyl-, molybdatetungstatephosphate

Endpoint summary

Description of key information

Pigment Blue 1 TOXICOKINETIC ANALYSIS:

 

There are no specific toxicokinetics or dermal absorption studies available for Pigment Blue 1 (Ethanaminium, N-[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthalenyl]methylene]-2,5-

cyclohexadien-1-ylidene]-N-ethyl-, molybdatetungstatephosphate). Therefore, following ECHA's Guidance on Information Requirements and Chemical Safety Assessment chapter R.7c [1] the main toxicokinetic properties of Pigment Blue 1 will be assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with Pigment Blue 1.

Pigment Blue 1 is a blue powder at room temperature with a molecular weight of ≥ 6600 ≤ 10500 g/mol. A log Pow of 1.0 was estimated from the single solubilities of the substance in n-octanol and water.

The vapour pressure could not be determined as the substance is a solid which undergoes exothermic decomposition starting at > 210 °C before melting.

The test substance is a UVCB with a purity of 100% (w/w).

 

Absorption

Oral route

Theoretically, based on its high molecular weight of ≥ 6600 ≤ 10500 g/mol, Pigment Blue 1 is not likely to be quantitatively absorbed in the GI tract since large molecules with a molecular weight above 1000 g/mol do not favour absorption. However, this assumption is not supported by the results of the repeated dose oral toxicity studies with Pigment Blue 1 indicating signs of systemic toxicity after exposure to the test substance. Following repeated exposure up to the limit dose of 1000 mg/kg bw/day, blue discoloration of faeces was observed, mortality, lower body weighs and histopathological findings in kidneys (tubular basophilia) were recorded at 300 and 1000 mg/kg/day indicating that the test item was able to pass the intestinal wall in toxicologically relevant amounts.

In conclusion, oral absorption is considered to be have occurred.

 

Inhalation route

The vapour pressure of Pigment Blue 1 could not be determined because exothermic decomposition of the substance starts at >210°C without melting. Therefore, the substance is not volatile, and inhalation to vapours is not relevant.

The particle size distribution of Pigmemt Blue 1 was determined by laser scattering/diffraction to be MMD = 46.17 µm (D10 = 10.41 µm, D90 = 145.16 µm), as the particle size of the material is 100& greater than 10 µm, all of the test substance, if inhaled, would be expected to be deposited in the upper respiratory tract and may be transported to the stomach via the mucociliary escalator. From here, it would be subjected to the same fate as any test substance that was dosed orally. Hazard identification and characterization for airborne exposures may, therefore, be extrapolated from data collected following oral administration. No experimental study was performed.

In conclusion, absorption via the inhalation route is assumed to be negligible.

 

Dermal route

Based on the molecular weight of > 6600 g/mol, low solubility in water, and absence of skin irritating properties, skin permeability of Pigment Blue 1 is expected to be very poor. In a local lymph node assay (OECD 429) studies with an analogous substances (used for a read-across assessment) no potential for skin sensitisation was noted and there were no signs of systemic toxicity indicating that absorption through the skin was unlikely to have occurred.

In conclusion, absorption via the dermal route is assumed to be negligible.

 

Distribution

As clinical signs were observed in a repeat dose oral toxicity studies with Pigment Blue 1, a distribution to potential target organs is considered to have occurred. Furthermore, there was indication of distribution to certain target organs ie kidney, based on macroscopic and histopathology examinations following repeated oral exposure of Pigment Blue 1. Due to the molecular weight of >> 6600 g/mol, distribution through aqueous channels and pores is restricted. An accumulative potential in adipose tissue can be excluded due to the estimated very low log Pow value of 1.0.

 

Metabolism

In the Ames test and the in vitro micronucleus test with Pigment Blue 1 no differences in regard to genotoxicity and cytotoxicity were seen in the presence or absence of metabolic activation systems. The results indicate that neither genotoxic nor more cytotoxic metabolites were formed in those test systems.

Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion.

 

Excretion

In the acute and repeated dose oral toxicity studies with Pigment Blue 1 in rats blue discoloration of feces was observed. These results indicate that a direct excretion via the feces without former GI tract absorption of the test substance represents the main excretion route after oral exposure.

Substance characteristics favourable for urinary excretion are low molecular weight (below 300 g/mol in the rat), good water solubility, and ionization at the pH of urine. Pigment Blue 1 does not fulfil these characteristics. Also, no discoloured urine was observed in the acute and repeated dose oral toxicity studies with Pigment Blue 1.

References

[1] ECHA (2017), Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, Version 3.0, June 2017

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential