N-[4-(aminocarbonyl)phenyl]-4-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]benzamide

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Expert statement

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Details on absorption:

A prerequisite for a relevant absorption is that the substance can be dissolved in either aque-ous (e.g., gastrointestinal fluid, blood plasma, sweat) or lipophilic (e.g., lipoproteins, lipid membranes, triglycerides) media or in both. PY 181 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that PY 181 becomes systemically bioavailable after oral, dermal or inhalation exposure.
Based on the acute oral toxicity study with C.I. Pigment Yellow 181in combination with its extremely low solubility absorption of toxicologically significant amounts via the gastrointes-tinal tract is considered unlikely, since C.I. Pigment Yellow 181did not show any effects. This is confirmed by experience with other pigments of the acetolone group, which did not cause any effects even after prolonged exposure in sub-chronic studies.
The skin sensitisation studies with C.I. Pigment Yellow 181indicate no local dermal bioavail-ability. Systemic availability also seems to be negligible after dermal exposure since no sys-temic signs of intoxication were seen after occlusive administration of 500 mg C.I. Pigment Yellow 181 per kg body weight in rabbits in the acute dermal irritation study.
Dermal absorption is, therefore, considered unlikely.
In the unlikely event of exposure to aerosolized pigment in respirable form, the substance is considered to behave like an inert dust. Therefore, the deposited pigment particles will mostly be cleared from the lung via the muco-cilliary transport. As the pigment will not dissolve in the lung surfactant, the only way the pigment can enter the body is via phagocy-tosis of pigment particles by lung macrophages followed by migration of the macrophages into the interstitium and into the draining lymph nodes. However, the internal dose deliv-ered via this mechanism can be considered negligible.

Details on distribution in tissues:

There is not information on the distribution of PY 181 itself, but Repeated Dose Toxicity Studies with analogue Acetolone-Pigments did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that the pigment either does not affect special organs as targets, i.e., is non-toxic, or is not distributed within the body in sig-nificant amounts. As indicated above, the physico-chemical parameters of the pigment sup-port the conclusion that the pigment is not absorbed into the body and thus does not become systemically available. There were also no other signs of deposition of the pigment in any organ including excretory organs), like the kidney, indicating that even exposure to high dos-es of these pigments does not lead to bioaccumulation in special compartments of the body. There is just one exception: The insoluble particles can b found in the lung after inhalation. This however is no sign of absorption and distribution but a deposition on the surface of first contact. This observation even indicates that the materials are not absorbed at all.
Based on the available information on absorption distribution of the test material in the body in significant amounts is unlikely and specific hotspots of distribution cannot be identified.
Thus, it is concluded, that C.I. Pigment Yellow 181 is not systemically available at relevant concentrations within the organism.
There were no signs of bioaccumulation of the test material. This view is supported by the physical-chemical properties (solubility in water and octanol).

Metabolites identified:

no

Metabolism:

Since the solution of the substance in cellular fluid or cellular membranes is a prerequisite for its metabolism, it is unlikely that the insoluble pigment becomes accessible for metabolizing systems in relevant amounts.

The results of the mutagenicity test provide useful indications for qualitative consideration of the metabolic fate of C.I. Pigment Yellow 181. In the mutagenicity test, the pigment proved to be non-mutagenic in the absence as well as in the presence of an exogenous metabolizing system, indicating that the pigment is not converted into toxic or genotoxic metabolites. This conclusion is also supported by the lack of any morphological and histopathological changes of organs involved in xenobiotic metabolism, such as the liver, in studies with analogue pigments. Furthermore, the missing skin or eye irritating or skin sensitizing properties argue against any interaction with biological material.

Therefore, C.I. Pigment Yellow 181 is considered to just pass through the intestinal tract without significant metabolism.

 

Excretion:

Considering the physico-chemical properties and the molecular structure and size of the material and the absence of any indication of absorption and/or metabolism it is assumed that excretion, if any, is likely to occur via faeces. This notion is confirmed by the discoloration of faeces observed in the acute study as the only alteration.

Conclusions:

Based on all available data, C.I. Pigment Yellow 181 does not exhibit conspicuous toxicoki-netic behaviour in the sense of accumulative and/or delayed effects with regard to the indi-vidual parameters absorption, distribution, metabolism and excretion.
The results from studies with dermal exposure indicate that C.I. Pigment Yellow 181 has a no relevant dermal absorptive potential. C.I. Pigment Yellow 181 is most probably not ab-sorbed from the gastrointestinal tract in significant amounts.
Indications of an intense metabolism or a bio-accumulative potential do not exist as no tox-icity occurred. Additionally, no systemic effects were observed in the repeated dose oral toxicity studies on analogue acetolone pigments, which points to no bio-accumulation poten-tial and complete excretion of all possibly available C.I. Pigment Yellow 181 and/or metabo-lites.

Executive summary:

Based on all available data, C.I. Pigment Yellow 181 does not exhibit conspicuous toxicokinetic behaviour in the sense of accumulative and/or delayed effects with regard to the individual parameters absorption, distribution, metabolism and excretion.

The results from studies with dermal exposure indicate that C.I. Pigment Yellow 181 has a no relevant dermal absorptive potential. C.I. Pigment Yellow 181 is most probably not absorbed from the gastrointestinal tract in significant amounts.

Indications of an intense metabolism or a bio-accumulative potential do not exist as no toxicity occurred. Additionally, no systemic effects were observed in the repeated dose oral toxicity studies on analogue acetolone pigments, which points to no bio-accumulation potential and complete excretion of all possibly available C.I. Pigment Yellow 181 and/or metabolites.

Description of key information

Based on all available data, C.I. Pigment Yellow 181 does not exhibit conspicuous toxicokinetic behaviour in the sense of accumulative and/or delayed effects with regard to the individual parameters absorption, distribution, metabolism and excretion.

The results from studies with dermal exposure indicate that C.I. Pigment Yellow 181 has a no relevant dermal absorptive potential. C.I. Pigment Yellow 181 is most probably not absorbed from the gastrointestinal tract in significant amounts.

Indications of an intense metabolism or a bio-accumulative potential do not exist as no toxicity occurred. Additionally, no systemic effects were observed in the repeated dose oral toxicity studies on analogue acetolone pigments, which points to no bio-accumulation potential and complete excretion of all possibly available C.I. Pigment Yellow 181 and/or metabolites.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential