Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment
Adequacy of study:
key study
Study period:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According REACH technical guidance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Evaluation of the available physico-chemical and toxicological data with the aim to describe toxicokinetic behaviour.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not applicable. Acronym for the substance name is APMODAN.
Radiolabelling:
no

Test animals

Species:
other: review of literature and data
Strain:
other: review of literature and data
Sex:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Substance is highly soluble in water so it is to be expected that the oral bioavailability, and thus the systemic exposure is high.
Type:
distribution
Results:
Distribution of the hydrophilic APMODAN will be limited to total body water. Therefore a volume of distribution of about 0.7 /kg is expected.
Type:
metabolism
Results:
After absorption, substance may be excreted unchanged in urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Uptake via inhalation make take place based on the vapour pressure. Since the bioavailability of dermal applied compounds can assumed to be zero for substances with a log Pow below -1 and over 5 or a relative molecular mass over 700 (2), it is not to be expected that APMODAN will be absorbed through the skin.
Details on distribution in tissues:
The plasma protein binding is expected to be low. Accumulation in fatty tissues is not anticipated.
Details on excretion:
Metabolism may occur via dealkylation of the tertiary nitrogen's. Direct glucuronidation and sulfatation at the nitrogen group can be expected. Extensive cleavage of the ether bond is anticipated followed by rapid sulfatation of glucuronidation of the resulting molecules.
The resulting metabolites will be excreted via bile and/or urine.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results not expected to be excreted in breast milk
Based on the expected kinetic behavior in the body, as described above, APMODAN will show a relatively high absorption after oral administration, mainly because of its high water solubility. Uptake via inhalation make take place. If absorption occurs, APMODAN can be excreted unchanged or be extensively metabolized in the liver and rapidly excreted via bile and/or urine. Therefore, accumulation in the body during prolonged exposure will be very low.
Executive summary:

Based on the expected kinetic behavior in the body, APMODAN will show a relatively high absorption after oral administration, mainly because of its high water solubility. Uptake via inhalation may take place. If absorption occurs, APMODAN can be excreted unchanged or be extensively metabolized in the liver and rapidly excreted via bile andlor urine. Therefore, accumulation in the body during prolonged exposure will be very low.