Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Expert statement
Adequacy of study:
other information
Study period:
2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Evaluation of available toxicologic data with regard to toxikokinetic behaviour
Justification for type of information:
REACH-regulations ask for an evaluation of available toxicologic data with regard to toxikokinetic behaviour in the absence of specific kinetic studies.

Data source

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

Materials and methods

Objective of study:
other: Evaluation and Assessment of the Basic Toxicokinetic Properties of C.I. Pigment Red 112
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Evaluation and Assessment of the Basic Toxicokinetic Properties of C.I. Pigment Red 112 based on available toxicologic and physical data
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
6335-46-2
Cas Number:
6335-46-2
IUPAC Name:
6335-46-2
Constituent 2
Chemical structure
Reference substance name:
3-hydroxy-N-(o-tolyl)-4-[(2,4,5-trichlorophenyl)azo]naphthalene-2-carboxamide
EC Number:
229-440-3
EC Name:
3-hydroxy-N-(o-tolyl)-4-[(2,4,5-trichlorophenyl)azo]naphthalene-2-carboxamide
Cas Number:
6535-46-2
Molecular formula:
C24H16Cl3N3O2
IUPAC Name:
3-hydroxy-N-(o-tolyl)-4-[(2,4,5-trichlorophenyl)azo]naphthalene-2-carboxamide
Test material form:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Based on the extremely low solubility bioavailability and, consequently, the internal dose delivered via all routes can be considered negligible.
Type:
distribution
Results:
As no absorption has been mesued nor is expected distribution is considered as not likely to occur
Type:
metabolism
Results:
As no absorption has been measued nor is expected metabolism is considered as not likely to occur
Type:
excretion
Results:
excretion, if any, is likely to occur via faeces

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. PR 112 can be considered insoluble because it has an extremely low solubility in water and n-octanol. Therefore, it is unlikely that PR 112 becomes systemically bioavailable after oral, dermal or inhalation exposure.
Based on the sub-acute oral toxicity study with C.I. Pigment Red112 absorption of toxico-logically significant amounts of C.I. Pigment Red 112 via the gastrointestinal tract is consid-ered unlikely, since it did not show any effects on inner organs and blood or urine.
The skin sensitisation studies with C.I. Pigment Red112 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 up to 5000 mg/kg bw. C.I. Pigment Red 112 per kg body weight in rabbits in the acute dermal toxicity and irrita-tion studies.
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 Red 112 did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that the pig-ment 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 the pigment does not lead to bioaccumulation in special 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 Red 112 is not systemically available at relevant con-centrations 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).
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 subacute study as the only alteration.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
This information is not available.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:
See chapter : Absorption

Applicant's summary and conclusion

Conclusions:
Based on all available data, C.I. Pigment Red 112 does not exhibit conspicuous toxicokinetic behaviour 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 112 has a no relevant dermal absorptive potential. C.I. Pigment Red 112 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 Red 112 and/or metabolites.
Executive summary:

Based on an evaluation of all available physico-chemical and toxicologic data, C.I. Pigment Red 112 does not exhibit conspicuous toxicokinetic behaviour in the sense of bioavailability, bio-accumulation 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 112 has a no relevant dermal absorptive potential. C.I. Pigment Red 112 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 bio-accumulation potential and complete excretion of all possibly available C.I. Pigment Red 112 and/or metabolites.