Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Expert Statement
Type of information:
other: Expert Statement
Study period:
2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expertstatement evaluating all available information with regard to toxicokinetic properties of the registered substance

Data source

Reference
Reference Type:
other: Expert statement
Title:
Evaluation and Assessment of the Basic Toxicokinetic Properties of C.I. Pigment Yellow 120
Author:
Clariant
Year:
2020
Report date:
2020

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl 2-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]terephthalate
EC Number:
252-650-1
EC Name:
Dimethyl 2-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]terephthalate
Cas Number:
35636-63-6
Molecular formula:
C21H19N5O7
IUPAC Name:
dimethyl 2-({2-oxo-1-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)carbamoyl]propyl}diazenyl)terephthalate
Test material form:
solid: nanoform

Results and discussion

Toxicokinetic / pharmacokinetic studies

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. PY120 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that PY120 becomes systemically bioavailable after oral, dermal or inhalation exposure.
Based on the acute oral toxicity study with C.I. Pigment Yellow 120 absorption of toxico-logically significant amounts via the gastrointestinal tract is considered unlikely, since C.I. Pigment Yellow 120 did not show any effects.
The skin sensitisation study with C.I. Pigment Yellow 120 indicates no local dermal bioa-vailability. Systemic availability also seems to be negligible after dermal exposure since no systemic signs of intoxication were seen after occlusive administration of 500 mg C.I. Pig-ment Yellow 120 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:
The toxicity studies with C.I. Pigment Yellow 120 did not indicate any relevant changes in any organs. This may indicate that the pigment either does not affect specific organs as tar-gets, i.e., is non-toxic, or is not distributed within the body in significant amounts. As indi-cated above, the physico-chemical parameters of the pigment support 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 doses of the pigment does not lead to bioaccumulation in specific compartments of the body.
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 120 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).
Details on 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 subacute study as the only alteration.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Since the dissolution 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 metabo-lizing systems in relevant amounts.
The results of the mutagenicity tests provide useful indications for qualitative consideration of the metabolic fate of C.I. Pigment Yellow 120. In the mutagenicity tests, the pigment proved to be non-mutagenic in the absence as well as in the presence of an exogenous me-tabolizing system, indicating that the pigment is not converted into toxic or genotoxic me-tabolites. Furthermore, the missing skin or eye irritating or skin sensitizing properties argue against any interaction with biological material.
Therefore, C.I. Pigment Yellow 120 is considered to just pass through the intestinal tract without significant metabolism.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:
Since the dissolution 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 metabo-lizing systems in relevant amounts.
The results of the mutagenicity tests provide useful indications for qualitative consideration of the metabolic fate of C.I. Pigment Yellow 120. In the mutagenicity tests, the pigment proved to be non-mutagenic in the absence as well as in the presence of an exogenous me-tabolizing system, indicating that the pigment is not converted into toxic or genotoxic me-tabolites. Furthermore, the missing skin or eye irritating or skin sensitizing properties argue against any interaction with biological material.
Therefore, C.I. Pigment Yellow 120 is considered to just pass through the intestinal tract without significant metabolism.

Applicant's summary and conclusion

Conclusions:
Based on all available data, C.I. Pigment Yellow 120 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 120 has a no relevant dermal absorptive potential. C.I. Pigment Yellow 120 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 acute oral toxicity study, which points to no bio-accumulation potential and complete excretion of all possibly available C.I. Pigment Yellow 120 and/or metabolites.
Executive summary:

Based on the available data base on C.I. Pigment Yellow 120 relevant information exists to make a qualitative evaluation of the toxicokinetic profile of this compound. This is in line with animal welfare considerations because additional animal tests can be avoided by such an evaluation.

 

The results of basic toxicity testing give no reason to anticipate unusual characteristics regarding the toxicokinetic properties of C.I. Pigment Yellow 120. The data indicate that there is no relevant dermal absorption. C.I. Pigment Yellow 120 is not absorbed from the gastro-intestinal tract in toxicologically significant amounts. Indications of a bio-accumulative potential as well as metabolism towards genotoxic sub-structures do not exist. Excretion of small amounts of possibly systemically available C.I. Pigment Yellow 120 and/or metabolites via faeces is likely.