4-[2-[4-[benzylmethyl(ethyl)amino]phenyl]vinyl]-1-(2-hydroxyethyl)pyridinium acetate

Endpoint summary

Description of key information

Toxicokinetics of C.I. Basic Orange 60

 

A toxicokinetic assessment for C.I. Basic Orange 60 has been made based on the physical and chemical properties of the substance and the available toxicity studies on the substance.

A substance can enter the body via the lungs, the gastrointestinal tract, and the skin. To determine the absorption rate, the different routes need to be assessed individually.

The size of the molecule, log Kow and water solubility are important factors in uptake and distribution of chemicals.

 

Basic Orange 60 is a basic dye. Basic dyes are cationic, water-soluble dyestuffs that have high affinity for mechanical and unbleached pulps with a large amount of acid groups in the fibre. Colouring is achieved by the reaction with these acid groups. Basic dyes are used for applications where lightfastness is less critical. This can be in wrapping paper, kraft paper, box board, news and other inexpensive packaging papers, but they are also suitable for calendar staining and surface colouring.

Based on the data generated for C.I. Basic Orange 60, it can be concluded that the log Kow is low (-0.27) and the water solubility is high (>1000 g/L). The molecular weight is 359.5 Da (as cation).

 

Oral absorption

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration.

(1) C.I. Basic Orange 60 has a high water solubility, therefore it is expected to dissolve into the gastrointestinal fluids, but uptake by passive diffusion is limited due to its low solubility in the GI lining.

(2) The molecular weight of the substance is favorable for absorption.

(3) The substance has a low log Kow, which makes the compound hydrophilic in nature.

(4) The substance is polar and this will limit uptake from the GI tract.

 

In the available repeated dose-reproduction study (Eurofins 2018 see dossier), the NOAEL of the substance was the highest dose tested (250 mg/kg/day). No treatment related findings for systemic and reproductive endpoints were found.

In an acute oral toxicity study the LD50 value was 1700 mg/kg bw. Effects observed included diarrhea, nausea and sedation. Macroscopy was without any findings in survivors and inconclusive due to orange discoloration in decedents (Bayer 1981, see dossier). 

Based on these results and the physico-chemical properties, absorption of the substance is expected to be low. The oral absorption is therefore set at 10% (default value). 

 

Dermal absorption

When the substance comes in contact with the skin, the first layer of the skin, the stratum corneum, forms a barrier for hydrophilic compounds. The substance has a log Kow of -0.27 and is very water soluble, suggesting that uptake in the stratum corneum will be limited. The polarity of the chromophore are expected to contribute further to a low absorption. The substance is a skin irritant and this could influence absorption. Some absorption is expected also because the substance is sensitizing to the skin.

 

According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in cases where the MW >500 and log Pow <-1 or >4. C.I. Basic Orange does not fulfil these criteria and therefore also in view of the irritant properties of the substance the dermal absorption is set at 50%.

 

Inhalation

The substance has a very low vapour pressure (see dossier) and is therefore not expected to evaporate and become available via inhalation. Moreover, aerosol formation is not expected from the current uses. Therefore exposure of the respiratory tract is not likely. If, however, the test substance would reach the tracheobronchial region, it may likely dissolve within the mucus lining the respiratory tract due to its high water solubility, but uptake would be very low because the high hydrophilicity will prevent passage via bio-membranes.

 

The inhalation route are considered not relevant as exposure route and are therefore not further considered.

 

Bioavailability and metabolism

 

BO60 is a highly viscous liquid. The substance shows no systemic toxicity for all of the end-points evaluated. The substance is irritating to the skin, eye damaging and a skin sensitizer.

As indicated above limited absorption of the substance is expected. If absorbed, no bioaccumulation is expected, as the aromatic rings in the molecule are expected to be oxidised or the pyrimidine ring to be reduced. Another possibility could be direct conjugation of the hydroxyl group. Based on the absence of toxicity in the available studies, the formation of toxic metabolites is not expected. This is also confirmed in the mutagenicity tests, where metabolic activation does not lead to increased toxicity (Eurofins 2017, see dossier).

 

Excretion

Excretion of unabsorbed C.I. Basic Orange 60 will be via the feces, but any substance or metabolites that are absorbed will be cleared via the kidneys after conjugation.

 

Conclusion

 

Absorption of C.I. Basic Orange 60 via the oral route is expected to be very limited. Dermal absorption could be expected based on the skin sensitization observed. After uptake the substance may be metabolized and conjugated before excretion via the kidney. Any unabsorbed substance will be excreted via the feces.

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

10