[2-[[2-cyano-3-[4-[ethylbenzylamino]phenyl]-1-oxoallyl]oxy]ethyl]trimethylammonium chloride

Endpoint summary

Description of key information

A toxicokinetic assessment for C.I. Basic Yellow 90 has been made based on the physical and chemical properties of the substance and the available toxicity studieson 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 Yellow 90 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 forC.I. Basic Yellow 90, it can be concluded that the log Kow is low (-0.30) and the water solubility is high (>1000 g/L). The molecular weight is 392 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 Yellow 90has 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 substancewas the highest dose tested (600 mg/kg/day). No treatment related findings for systemic and reproductive endpoints were found. In an older 90-day study (Bayer 1984 see dossier), the substance, when applied via drinking water, induced irritation of the GI tract at 0.3% (equivalent to ca 240 and 300 mg/kg bw in males and females). At this dose level 7/20 males died. Other effects at 0.3% in males included reduced food and water intake, decreased red and white blood cell numbers, decreased platelets, decreased creatinine, glucose and cholesterol levels and increased thyroid, kidney and liver weight. In females at 0.3% similar effects on blood parameters were found, as well as an increased kidney and decreased lung weights, but no mortality. None of the effects were related to histopathological findings. The NOAEL as derived from this study is 84 and 96 mg/kg bw for males and females. 

In two acute oral toxicity studies LD50 values of > 3500 mg/kg bw were found (values corrected for the purity of the tested formulations, Bayer 1985, 1983 see dossier). Effects seen were on the GI-tract and might be related to the corrosivity of the tested formulation (acetic acid present).

The damage to the GI tract lining due to this corrosivity may lead to higher actual uptake than expected based on the physicochemical characteristics of the substance.

 

Based on the study results and the potential influence of the corrosiveness as discussed above, some absorption of the test substance is anticipated. The oral absorption is therefore set at 50%. Only after prolonged exposure or at high doses the absorption could be higher due to disruption of the GI-tract lining.

 

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 -0.30 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.

Skin irritation and corrosion studies show that the substance is corrosive. This may lead to additional uptake via the potentially damaged skin and systemic exposure.

 

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 Yellow 90 does not fulfil these criteria and therefore also in view of the corrosivity of the substance the dermal absorption is set at 100%.

 

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. It could, however, argued that the acetic acid present is easily taken up, but this is unlikely to contribute significantly to systemic toxicity.Based on these considerations, for risk assessment purposes the inhalation absorption of the chromophore is expected to be low, but could be enhanced by effects of acetic acid.

 

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

 

Bioavailability and metabolism

 

BY90 is a yellow organic liquid UVCB. The substance shows no systemic toxicity for all of the end-points evaluated. The substance is, however, corrosive.

As indicated above absorption of the substance is expected. After absorption, no bioaccumulation is expected, as the substance is expected to hydrolyze (via esterases or at low pH) and conjugated. The nitrile group could be hydrolyzed, oxidized or reduced, but these mechanisms were mainly identified in micro-organisms (Rhamakrishna et al. J Scientific & Industrial Research 58, 1999 925-947). 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 (Bayer 2002 and Eurofins 2017, see dossier). The effects seen in the GI-tract at high doses or prolonged exposure in the acute and repeated dose studies seem to be related to the corrosivity of the substance.

 

Excretion

Excretion of unabsorbed C.I. Basic Yellow 90 will be via the feces, but any substance or metabolites that are absorbed will be cleared via the kidneys after conjugation.

 

Conclusion

 

C.I. Basic Yellow 90 is corrosive and this will enhance absorption potential via the oral and dermal route. 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 (%):

50

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

10