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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement
Adequacy of study:
key study
Study period:
2021
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Evaluation of all available data with regard to toxico-kinetic properties.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Objective of study:
absorption
distribution
excretion

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(4-nitrophenyl)azo]-3-oxobutyramide
EC Number:
258-221-5
EC Name:
N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(4-nitrophenyl)azo]-3-oxobutyramide
Cas Number:
52846-56-7
Molecular formula:
C17H14N6O5
IUPAC Name:
2-[(4-nitrophenyl)diazenyl]-3-oxo-N-(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)butanamide
Test material form:
solid: bulk

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. Pigment Orange 62 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that Pigment Orange 62 becomes systemically bioavailable after oral, dermal or inhalation exposure.
Based on the acute and subacute oral toxicity studies with C.I. Pigment Orange 62 in combi-nation with its extremely low solubility absorption of toxicologically significant amounts via the gastrointestinal tract is considered unlikely, since C.I. Pigment Orange 62 did 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 Orange 62 indicate 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 Orange 62 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 measured information on the distribution of Pigment Orange 62 itself, but Re-peated Dose Toxicity Studies with Pigment Orange 62 and 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 significant amounts. As indicated 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 these pigments does not lead to bio-accumulation in special compartments of the body. There is just one exception: The insoluble particles can be 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 material is 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 Orange 62 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 ma-terial 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.

Metabolite characterisation studies

Details on metabolites:
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 metabo-lizing systems in relevant amounts.
The results of the mutagenicity test provide useful indications for qualitative consideration of the metabolic fate of C.I. Pigment Orange 62. In the mutagenicity test, 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. This conclusion is also supported by the lack of any morphological and histo-pathological changes of organs involved in xenobiotic metabolism, such as the liver, in stud-ies with analogue pigments. Furthermore, the missing skin or eye irritating or skin sensitiz-ing properties argue against any interaction with biological material.
Therefore, C.I. Pigment Orange 62 is considered to just pass through the intestinal tract without significant metabolism.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:
not bio-accessible

Applicant's summary and conclusion

Conclusions:
Based on all available data, C.I. Pigment Orange 62 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 Orange 62 has a no relevant dermal absorptive potential. C.I. Pigment Orange 62 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 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 Orange 62 and/or metabo-lites.
Executive summary:

Based on all available data, C.I. Pigment Orange 62 does not exhibit conspicuous toxicokineticbehaviour 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 Orange 62 has a no relevant dermal absorptive potential. C.I. Pigment Orange 62 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 Orange 62 and/or metabolites.