Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment based on available physico-chemical data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Assessment based on available physico-chemical data

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Assessment based on available physico-chemical data
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
particle size not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
see "any other information on results incl. tables" section
Type:
distribution
Results:
see "any other information on results incl. tables" section
Type:
metabolism
Results:
see "any other information on results incl. tables" section
Type:
excretion
Results:
see "any other information on results incl. tables" section

Any other information on results incl. tables

Absorption:

Based on above data the substance may not be absorbed through the skin in relevant amounts as the Log POWis below the lower threshold of -1 (molecular weight < 500 g/Mol, -1 < log POW< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRETORATE-GENERAL: Guidance Document on Dermal Absorpiton Sanco/222/2000 rev. 7 19 March 2004).

For exposure assessments a default value of 10 % of absorption after dermal exposure may be appropriate.

The uptake after direct inhalation of the solid substance may be of significant relevance due to findings in an acute inhalation toxicity study. Additionally the substance is marketed as powder and a granulometric studies is not available. For Risk assessment purposes a value of 100 % absorption after inhalation may be appropriate. Uptake by inhalation after evaporation is unlikely, the substance is a solid at room temperature decomposes upon heating together with a very low vapour pressure.

The absorption after oral ingestion cannot be calculated due to lack of data; by default an absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

 


Distribution:

The substance is highly hydrophilic therefore distribution to lipophilic body tissues is unlikely. The limited stability together with the high hydrophilicity likely excludes bio accumulation. There are no further information available therefore a more detailed description is futile.

 

 

 

Metabolism and Excretion:

Taking into account the structural elements of the formula it follows that the unchanged substance is a substrate for Phase I Enzymes, especially the imidazole residues. Due to the low stability of the substance, it is likely that decomposition occurs before the substance reaches the metabolic organs. However, the imidazole residues is not primarly effected by the decomposition mechanism (radical formation and release of molecular nitrogen from the central azo Group).

Subsequent to decomposition and Phase I metabolism, the different Phase-II aducts can be formed. There is no indication whether a Glutathion-, Sulphate-, Acetate- or Glucuronate adduct is favoured.

 

The high water solubility of the substance indicates urinary excretion as the most relevant way of excretion for the unchanged substance.

Another relevant pathway for exretion may be by feces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.

Excretion by exhalation does not seem to be relevant.

 

 

Applicant's summary and conclusion

Conclusions:
An assessment based on available physico-chemical data is performed.
The relevant results are taken for risk assessment purposes:
dermal absorption: 10%
inhalative absorption: 100%
oral absorption: 100 %
Bioaccumulation: unlikely