Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Expert statement
Type of information:
other: Expert Statement
Adequacy of study:
supporting study
Study period:
Study completion date - 07 August 2002.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expert statement

Data source

Reference
Reference Type:
other: Expert statement
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Principles of method if other than guideline:
Basic toxicokinetic assessment based on phys.-chem. properties and available toxicological data.
GLP compliance:
no

Test material

Constituent 1
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Specific details on test material used for the study:
Identity: FAT 40810/A
Batch: WP 6/02
Purity: approx. 75 %
Appearance: Solid, dark brownish powder
Expiration date: 12 December 2010
Storage: At room temperature at about 20 °C

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables


ABSORPTION AND METABOLISM:


The findings of the 28-day toxicity study may indicate that despite its polarity, the substance may be - at least partially - absorbed in the gut and metabolized. After oral uptake into the gastrointestinal duct an ionization of the substance has to be considered at low pH (e.g. protonization of amine groups), which may influence the location of resorption. Resorption may make take place at low ionization grade at higher pH in the small intestine. Further, based on the above mentioned hydrolysis results it might be assumed that the substance is not significantly hydrolyzed at low pH before absorption in the gut. Furthermore, the substance may partially be hydrolyzed in the small intestine based on the above mentioned hydrolysis results at pH 7 and 9. Metabolic degradation such as e.g.enzymatic reduction of the azo-groups by gut bacteria, and hydroxylation of alkyl and aromatic groups are conceivable. Due to its hydrophilicity and low log Pow it is not probable that the substance is taken up through the skin. The MMD of 5.7 µm indicates a high proportion of respirable particles, therefore, inhalative uptake has to be taken into consideration.



 


DISTRIBUTION AND EXCRETION:


The substance is anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. The clinical biochemistry findings in the mid-dose and high-dose level groups of the 28-day toxicity study corroborate this assumption. Since the substance is hydrophilic and ionizable, and has a low log Pow an accumulation in fatty tissue is not to be expected.

Applicant's summary and conclusion

Conclusions:
Reactive Orange 140 is expected to be absorbed to some extent from the gastrointestinal tract, while absorption through skin will be low. The MMD of 5.7 µm indicates a high proportion of respirable particles, therefore, inhalation uptake has to be taken into consideration. The substance is anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. Since the substance is hydrophilic and ionizable, and has a low log Pow, an accumulation in fatty tissue is not to be expected.
Executive summary:

ABSORPTION AND METABOLISM:


The findings of the 28-day toxicity study may indicate that despite its polarity, the substance may be - at least partially - absorbed in the gut and metabolized. After oral uptake into the gastrointestinal duct an ionization of the substance has to be considered at low pH (e.g. protonization of amine groups), which may influence the location of resorption. Resorption may make take place at low ionization grade at higher pH in the small intestine. Further, based on the above mentioned hydrolysis results it might be assumed that the substance is not significantly hydrolyzed at low pH before absorption in the gut. Furthermore, the substance may partially be hydrolyzed in the small intestine based on the above mentioned hydrolysis results at pH 7 and 9. Metabolic degradation such as e.g.enzymatic reduction of the azo-groups by gut bacteria, and hydroxylation of alkyl and aromatic groups are conceivable. Due to its hydrophilicity and low log Pow it is not probable that the substance is taken up through the skin. The MMD of 5.7 µm indicates a high proportion of respirable particles, therefore, inhalation uptake has to be taken into consideration.



 


DISTRIBUTION AND EXCRETION:


The substance is anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. The clinical biochemistry findings in the mid-dose and high-dose level groups of the 28-day toxicity study corroborate this assumption. Since the substance is hydrophilic and ionizable, and has a low log Pow an accumulation in fatty tissue is not to be expected.