Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Evaluation of avalable data
Type of information:
other: Expert statement
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
no guideline required
GLP compliance:
no
Remarks:
Not required

Test material

Constituent 1
Chemical structure
Reference substance name:
2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.03,19.05,17.06,14.07,12.023,25.024,32.025,30]hexatriaconta-1(36),2,5,7,9,11,14,16,18,20,23,25,27,29,32,34-hexadecaene
EC Number:
606-790-9
Cas Number:
215247-95-3
Molecular formula:
C34H22Cl2N4O2
IUPAC Name:
2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.03,19.05,17.06,14.07,12.023,25.024,32.025,30]hexatriaconta-1(36),2,5,7,9,11,14,16,18,20,23,25,27,29,32,34-hexadecaene
Test material form:
liquid: viscous

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Absorption is not likely
Type:
distribution
Results:
No indications of disstribution or accumulation have been detected
Type:
metabolism
Results:
No metabolites have been identified
Type:
excretion
Results:
The material is likely to just pass through the intestinal tract after oral administration

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 Violet 23 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that Pigment Violet 23 becomes systemically bioavailable after oral, dermal or inhalation ex-posure.
Based on the sub-acute oral toxicity study with C.I. Pigment Violet 23 absorption of toxico-logically significant amounts via the gastrointestinal tract is considered unlikely, since C.I. Pigment Violet 23 did not show any effects on inner organs and blood or urine.
The skin sensitisation studies with C.I. Pigment Violet 23 indicate no local dermal bioavaila-bility. 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 Violet 23 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 mucocilliary transport. As the pigment will not dis-solve in the lung surfactant, the only way the pigment can enter the body is via phagocyto-sis 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 Repeated Dose Toxicity Study with C.I. Pigment Violet 23 did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that the pig-ment either does not affect specific 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 the pigment does not lead to bioaccumulation in specific compart-ments 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 Violet 23 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 subacute study as the only alteration.

Metabolite characterisation studies

Metabolites identified:
not measured

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:
A prerequisite for a relevant bio-accessability is that the substance can be dissolved in either aqueous (e.g., gastrointestinal fluid, blood plasma, sweat) or lipophilic (e.g., lipoproteins, lipid membranes, triglycerides) media or in both. Pigment Violet 23 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that Pigment Violet 23 becomes systemically bioavailable after oral, dermal or inhalation ex-posure.

Applicant's summary and conclusion

Conclusions:
Based on all available data, C.I. Pigment Violet 23 does not exhibit conspicuous toxicokinet-ic behaviour in the sense of accumulative and/or delayed effects with regard to the individu-al parameters: absorption, distribution, metabolism and excretion.
The results from studies with dermal exposure indicate that C.I. Pigment Violet 23 has a no relevant dermal absorptive potential. C.I. Pigment Violet 23 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 subacute oral toxicity study, which points to no bio-accumulation potential and complete excretion of all possibly available C.I. Pigment Violet 23 and/or metabolites.
Executive summary:

Based on the available data base on C.I. Pigment Violet 23 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 substance is available in nano-form.

The results of basic toxicity testing give no reason to anticipate unusual characteristics regarding the toxicokinetics of C.I. Pigment Violet 23. The data indicate that there is no relevant dermal absorption. C.I. Pigment Violet 23 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 Violet 23 and/or metabolites via faeces is likely.

Categories Display