Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatephosphates

Endpoint summary

Description of key information

TOXICOKINETIC ANALYSIS:

 

There are no specific toxicokinetics or dermal absorption studies available for Pigment Violet 3:4 or the read-across substance PV3 PTM. Therefore, in line with ECHA's Guidance on Information Requirements and Chemical Safety Assessment chapter R.7c [1] the main toxicokinetic properties of Pigment Violet 3:4 are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance.

 

Pigment Violet 3:4 is a very dark purple powder at room temperature with a molecular weight of ≥ 3800 ≤ 7300 g/mol. A log Pow of 0.1 was estimated from the estimates of solubilities of the substance in n-octanol and water.

 

The vapour pressure could not be determined as the substance is a solid which decomposes at > 200 °C before melting.

 

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

 

Absorption

 

Oral route

 

Based on its high molecular weight of ≥ 3800 ≤ 7300 g/mol Pigment Violet 3:4 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. This assumption is supported by the results of the acute and repeated dose oral toxicity studies with Pigment Violet 3 PTM indicating no signs of systemic toxicity after exposure to the test substance. Following repeated exposure up to the limit dose of 1000 mg/kg bw/day, violet discoloration of faeces was observed but no toxicological effects were reported for other organs or tissues including the lymphatic system indicating that the violet test item was not able to pass the intestinal wall in toxicologically relevant amounts.

 

In conclusion, oral absorption is considered to be very low.

 

Inhalation route

 

The vapour pressure of Pigment Violet 3:4 could not be determined because the substance decomposes at >200°C without melting. Therefore, the substance is not volatile, and inhalation to vapours is not relevant.

 

The particle size distribution of Pigment Violet 3 PTM was determined by laser scattering/diffraction to be VMD = 54.92 µm (D10 = 15.77 µm, D50 = 50.98µm and D90 = 98.20 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 > 500 g/mol, low solubility in water, and absence of skin irritating properties, skin permeability of Pigment Violet 3:4 is expected to be very poor. However, Pigment Violet 3:4 showed a potential for skin sensitisation in the local lymph node assay (OECD 429) suggesting a certain systemic availability of Pigment Violet 3:4.

 

Additionally no indication of systemic availability (i.e. systemic toxicity or discoloured urine) was observed in the LLNA with Pigment Violet 3:4 in mice.

 

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

 

Distribution

 

Since no clinical signs were observed in acute oral toxicity study with Pigment Violet 3:4 and the analogous substance Pigment Violet 3 PTM, a distribution to potential target organs seems unlikely. Furthermore, there was no indication of distribution to certain target organs based on macroscopic and histopathology examinations following repeated oral exposure of the analogous structure Pigment Violet 3 PTM. Due to the molecular weight of >3800 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 solubility in water and n-octanol (value of <0.1 mg/L).

 

 Metabolism

 

In the Ames test and the in vitro gene mutation test in mammalian cells with Pigment Violet 3:4 and the in vitro micronucleus test with Pigment Violet 3 PTM no remarkable 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 Violet 3:4 in rats violet 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 Violet 3:4 does not fulfil these characteristics. Also, no discoloured urine was observed in the acute and repeated dose oral toxicity studies with Pigment Violet 3:4.

 

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:

no bioaccumulation potential