Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A well documented publication. However, the study was not conducted in accordance with the OECD guideline or with the GLP Regulation.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline available
GLP compliance:
no

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): MTHPA
- Stability under test conditions: stable
- Storage condition of test material: -20 °C
Radiolabelling:
no

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no details given

Administration / exposure

Vehicle:
other: urine
Details on exposure:
TEST SITE
- Time after start of exposure: 3h

Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
30-110 ng/ml
No. of animals per sex per dose / concentration:
10 urines
Control animals:
no
Positive control reference chemical:
not applicable
Details on study design:
no details given
Details on dosing and sampling:
PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: urine

METABOLITE CHARACTERISATION STUDIES
- Method type(s) for identification: GC-FID, GC-MS
column: fused-silica capillary column (30 m x 0.25 mm I.D.)
DB-5 phase and film thickness: 0.25 µm
Injection: 250 degree C
column: 110 degree C/1 min, 6 degree C /min to 140 degree C and keeping 3 min, 40 degree C/2 min
Statistics:
no details given

Results and discussion

Preliminary studies:
no details given

Toxicokinetic / pharmacokinetic studies

Details on absorption:
In humans, the substance is taken up through the respiratory way by inhalation.
Toxicokinetic parameters
Toxicokinetic parameters:
half-life 1st: 3-6 hours

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
In humans, the substance is metabolized to the corresponding dicarboxylic acids and excreted in urine. The half-times of the urine concentration of these dicarboxylic acids were 3-6 hr.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The half-times of the urine concentration of these dicarboxylic acids were 3-6 hr.
Executive summary:

In humans, tetrahydromethylphthalic anhydride (MTHPA) is taken up through the respiratory way by inhalation and is metabolized to the corresponding di-carboxylic acids and excreted in urine. The half-times of the urine concentration of these di-carboxylic acids were 3-6 hr.