4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Expert statement based on available data

Type of information:

other: Expert statement based on available data

Study period:

2022

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

absorption

bioaccessibility (or bioavailability)

distribution

excretion

metabolism

toxicokinetics

other:

Qualifier:

no guideline required

Principles of method if other than guideline:

Available physical, chemical and toxicological data were evaluated with regard to information of toxicokinetic behaviour of the registered substance

GLP compliance:

no

Type:

absorption

Results:

Pigment Red 170 is most likely not sufficiently bioavailable after oral dermal or inhalation exposure to create any (adverse) effects.

Details on absorption:

A prerequisite for a relevant absorption 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. C.I. Pigment Red 170 can be considered insoluble because it has an extremely low solubility in water (11.9 µg/L) and n-octanol (225 µg/L). Therefore, it is unlikely that C.I. Pigment Red 170 becomes systemically bioavailable after oral, dermal or inhalation exposure. The available data on bioavailability confirm this notion.
Based on the sub-chronic oral toxicity study absorption of toxicologically significant amounts of C.I. Pigment Red 170 via the gastrointestinal tract is considered unlikely, since it did not show any effects on inner organs and blood or urine.
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 mostly 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 pigment particles by lung macrophages followed by migration of the macrophages into the interstitium and into the draining lymph nodes. However, the internal dose delivered via this mechanism can be considered negligible. The acute inhalation toxicity study showing no adverse effect at the highest technical achievable concentration of ca.1.6 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 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 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.

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 Red 170 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

Enzymatic activity measured:

No

Conclusions:

Based on all available data, C.I. Pigment Red 170 does not exhibit conspicuous toxico-kinetic behavior 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 Red 170 has no relevant dermal absorptive potential. C.I. Pigment Red 170 is most probably not absorbed from the gastrointestinal tract in significant amounts.
Indications of metabolism or a bio-accumulative potential do not exist as no toxicity occurred. Additionally, no systemic effects were observed in the subacute oral toxicity study, which points to no bioaccumulation potential and to complete excretion of all possibly available C.I. Pigment Red 170 and/or metabolites.

Executive summary:

Based on the available database on C.I. Pigment Red 170 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 about the toxico-kinetics of C.I. Pigment Red 170. The data indicate that there is no relevant dermal absorption. C.I. Pigment Red 170 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 170 and/or metabolites via faeces is likely.

Description of key information

Based on the available database on C.I. Pigment Red 170 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 about the toxico-kinetics of C.I. Pigment Red 122. The data indicate that there is no relevant dermal absorption. C.I. Pigment Red 170 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 170 and/or metabolites via faeces is likely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential