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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement
Adequacy of study:
supporting study
Study period:
2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Evaluation of available data with regard to toxico-kinetics
Objective of study:
other: Evaluation and Assessment of the Basic Toxicokinetic Properties of C.I. Pigment Red 202
Qualifier:
no guideline available
Principles of method if other than guideline:
Available toxicologic data were evaluated with regard to toxico-kinetic properties.
GLP compliance:
no
Details on absorption:
A prerequisite for a relevant absorption is that the substance can be dissolved in either aque-ous (e.g., gastro-intestinal fluid, blood plasma, sweat) or lipophilic (e.g., lipoproteins, lipid membranes, triglycerides) media or in both. C.I. Pigment Red 202 can be considered insolu-ble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that C.I. Pigment Red 202 becomes systemically bioavailable after oral, dermal or inhalation exposure. The available data on bio-availability confirm this notion.
Based on the sub-chronic oral toxicity study absorption of toxicologically significant amounts of its structural analogue via the gastrointestinal tract is considered unlikely, since it did not show any effects on inner organs and blood or urine. No pigment was detected in liver or blood samples.
The skin sensitization as well as the acute dermal data indicate neither local nor systemic dermal bioavailability. Dermal absorption, therefore, is 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 most-ly be cleared from the lung via the mucocilliary transport. As the pigment will not dissolve in the lung surfactant, the only way the pigment can enter the body is via phagocytosis of pig-ment particles by lung macrophages followed by migration of the macrophages into the inter-stitium and into the draining lymph nodes. However, the internal dose delivered via this mechanism can be considered negligible. The acute inhalation toxicity study of its structural analogue showing no adverse effect at the highest technical achievable concentration of ca. 3 mg/L strongly supports this view
Details on distribution in tissues:
The Repeated Dose Toxicity Study did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that the pigment either does not affect spe-cific 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 systemi-cally available. There were also no other signs of deposition of the intensely colored 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 special compartments of the body. No traces of pigment were found in samples of dried blood and liver tissue by analysis via HPLC with a limit of detection below 1.5 ppm.
Key result
Transfer type:
secretion via gastric mucosa
Observation:
no transfer detectable
Details on excretion:
Taking into account the physico-chemical properties and the molecular structure of the mate-rial and the absence of any indication of absorption and/or metabolism it is assumed that ex-cretion, if any, is likely to occur via faeces. This notion is confirmed by the discoloration of faeces observed in the subchronic study as the only alteration.

Metabolites identified:
not measured
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 metaboliz-ing systems in relevant amounts.
The results of the mutagenicity tests provide useful indications for qualitative consideration of the metabolic fate of C.I. Pigment Red 202. In the mutagenicity tests, 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 the Repeated Dose Toxicity Study. Furthermore, the missing skin or eye irritating or skin sensitizing properties argue against any interaction with biological material.

Therefore, C.I. Pigment Red 202 is considered to just pass through the intestinal tract with-out significant metabolism.
Bioaccessibility (or Bioavailability) testing results:
See chapter: Absorption
Conclusions:
Based on all available data, there were no signs of significant bioavailability of pigment red 202.
Executive summary:

 


Based on the available database on C.I. Pigment Red 202 relevant information exists to make a qualitative evaluation of the toxico-kinetic 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 with regard to the toxico-kinetics of C.I. Pigment Red 202. The data indicate that there is no relevant dermal absorption. C.I. Pigment Red 202 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 Red 202 and/or metabolites via faeces is likely.

Description of key information

Based on the available database on C.I. Pigment Red 202 relevant information exists to make a qualitative evaluation of the toxico-kinetic 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 with regard to the toxico-kinetics of C.I. Pigment Red 202. The data indicate that there is no relevant dermal absorption. C.I. Pigment Red 202 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 Red 202 and/or metabolites via faeces is likely.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information