Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Expert Judgement
Type of information:
other: Expert Judgement
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: expert statement
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Expert statement
Principles of method if other than guideline:
Rational argumentation based in physico-chemical properties of TODI and read-across from similar substance

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Radiolabelling:
other: not applicable

Test animals

Details on test animals and environmental conditions:
not applicable

Administration / exposure

Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
not applicable
No. of animals per sex per dose:
not applicable
Positive control:
not applicable
Details on study design:
not applicable
Details on dosing and sampling:
not applicable
Statistics:
not applicable

Results and discussion

Preliminary studies:
not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Data on the absorption or the metabolic fate and thus information on the toxicokinetics in humans of absorbed TODI is very limited.
No information is available on the toxicokinetics of TODI or e.g. "MDI" (methylene diphenyl diisocyanate, similar compound to TODI) following oral exposure in animals. But due to its high reactivity, orally ingested TODI will undergo spontaneous hydrolysis upon reaching the stomach as degradation products that are insoluble in water and thus TODI is not likely to cross gastrointestinal-tract membranes. Taken together, absorption in the gastrointestina-tract of TODI and consequently bioavailability is rather unlikely.
Details on distribution in tissues:
no data available
Details on excretion:
Excretion is likely to occur in form of GSH-conjugates. It is assumed to appear mainly via faeces (similar as shown in a study with MDI: 5% via urine and 79% in faeces).

Metabolite characterisation studies

Details on metabolites:
no data available

Bioaccessibility

Bioaccessibility testing results:
no data available

Any other information on results incl. tables

No tendency for bioavailability and bioaccumulation is expected

Applicant's summary and conclusion