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Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement, derived from available data
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Annex VIII requires an expert statement evaluating all available information with respect to the kinetic profile (ADME) of the test item

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Evaluation of ADME related information from physico-chemical, toxcological and eco-toxicological studies available.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrasodium [μ-[3-[[2-amino-5-hydroxy-6-[(2-hydroxy-5-nitro-3-sulphophenyl)azo]-7-sulpho-1-naphthyl]azo]-2-hydroxy-5-sulphobenzoato(8-)]]dichromate(4-)
EC Number:
276-538-7
EC Name:
Tetrasodium [μ-[3-[[2-amino-5-hydroxy-6-[(2-hydroxy-5-nitro-3-sulphophenyl)azo]-7-sulpho-1-naphthyl]azo]-2-hydroxy-5-sulphobenzoato(8-)]]dichromate(4-)
Cas Number:
72252-58-5
Molecular formula:
C23H8Cr2N6O16S3.4Na
IUPAC Name:
tetrasodium [μ-[3-[[2-amino-5-hydroxy-6-[(2-hydroxy-5-nitro-3-sulphophenyl)azo]-7-sulpho-1-naphthyl]azo]-2-hydroxy-5-sulphobenzoato(8-)]]dichromate(4-)
Radiolabelling:
other: not required (Theoretical consideration)

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Based on the subacute (28-day) oral toxicity study absorption of toxicologically significant amounts of Aluminium Black 2 LW via the gastrointestinal tract has to be assumed since obvious discoloration of inner organs was observed throughout the body. Most prominent were discolorations of digestive tract, liver, kidney, and lymph nodes.
Systemic availability seems to be negligible after dermal exposure since no systemic signs of intoxication were seen after occlusive administration of 2000 mg Aluminium Black 2 LW per kg body weight in rats in the acute dermal toxicity study. Indications of a significant dermal absorptive potential were also not revealed by testing for primary irritation in rabbits. The notion of very limited dermal absorption is also corroborated by the very high water solubility of more than 1000 g/L.
Details on distribution in tissues:
Based on the results of the subacute oral toxicity study discolorations were observed in the digestive tract (lumen and wall), liver, kidney, lymph nodes, and testes. Thus it can be concluded, that Aluminium Black 2 LW is absorbed through the gastrointestinal tract and systemically available within the organism. Histopathological findings indicate a deposition of the dye mainly in interstitial macrophages of the affected tissues.
There were no signs of bioaccumulation of the test material although the dose-response-relationship of the macroscopic as well as the microscopic discolorations after dosing in the subacute toxicity study indicates some retention of the dye. This view is supported by the physical-chemical properties (high solubility in water) and the molecular structure.
Details on excretion:
Taking into account the physico-chemical properties and the molecular structure of the dye it can be assumed that the main route of excretion will be the kidney. Nevertheless, most of the dose is expected to just pass through the digestive tract without being absorbed. This notion is confirmed by the discoloration of faeces and kidneys observed in the subacute study.

Metabolite characterisation studies

Details on metabolites:
Aluminium Black 2 LW proved to be inactive in the Ames-test with and without exogenous metabolic activation. It was not genotoxic in the HPRT and chromosomal aberration assay in vitro. This indicates that Aluminium Black 2 LW is not metabolically active. Metabolites, if any are formed, are not more toxic than the parent compound. Modelling of the metabolic fate of the test material using NEXUS-METEOR did also no give any indication of probable metabolism.
No effects were seen in the subacute study except for a discoloration of tissues histologically allocated to tissue macrophages. No functional or structural impairments were detected. Therefore, Aluminium Black 2 LW is considered to just pass through the organism without significant metabolism. The only interaction being some binding to bio-molecules giving rise to the deposition observed in macrophages. Depending on the dose the capacity of the excretion mechanisms may become exhausted leading to a temporary deposition of the dye in tissue macrophages.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:
Based on the results of the subacute oral toxicity study discolorations were observed in the digestive tract (lumen and wall), liver, kidney, lymph nodes, and testes. Thus, it can be concluded, that Aluminium Black 2 LW is absorbed through the gastrointestinal tract and systemically available within the organism. Histopathological findings indicate a deposition of the dye mainly in interstitial macrophages of the affected tissues.
There were no signs of bioaccumulation of the test material although the dose-response-relationship of the macroscopic as well as the microscopic discolorations after dosing in the subacute toxicity study indicates some retention of the dye. This view is supported by the physical-chemical properties (high solubility in water) and the molecular structure

Applicant's summary and conclusion

Conclusions:
Based on all available data, Aluminium Black 2 LW 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 do not indicate that Aluminium Black 2 LW has a definite dermal absorptive potential. Aluminium Black 2 LW is absorbed from the gastrointestinal tract in significant amounts.
Indications of an intense metabolism or a bio-accumulative potential do not exist as no delayed toxicity occurred. Additionally no increase in severity of systemic effects was observed in the subacute oral toxicity study, which also points to no bio-accumulation potential as well as to excretion of Aluminium Black 2 LW and/or metabolites
Executive summary:

Based on the available toxicological data on Aluminium Black 2 LW 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 results of basic toxicity testing give no reason to anticipate unusual characteristics with regard to the toxicokinetics of Aluminium Black 2 LW. The data indicate that there is no relevant dermal absorption. On the other hand, Aluminium Black 2 LW is absorbed from the gastro-intestinal tract in toxicologically significant amounts. Indications of a bio-accumulative potential as well as a metabolism towards genotoxic sub-structures do not exist. Excretion of systemically available Aluminium Black 2 LW and/or potential metabolites via the kidney can be assumed.

 

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