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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Published article describing the metabolism and kinetics of radiolabelled DPM.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Objective of study:
excretion
Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
14C-DPM 7.0 mCi/mmol (93.2% purity, secondary secondary isomer)
unlabelled DPM : 98% purity.
Radiolabelling:
yes
Remarks:
14C-DPM

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
Single exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
1289 mg/kg`
No. of animals per sex per dose:
3 males
Control animals:
no
Positive control:
Not applicable
Details on study design:
Expired air and excreta were monitored for 48 hours.
Details on dosing and sampling:
Three male rats were each given, by oral gavage, radiolabelled 14-C DPM with an activity of 5 uCi in a volume which did not exceed 0.5 mL. The dose was 1289 mg/kg DPM. Radiolabel was determined in feces, carcass, liver, kidney, blood, and brain.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
93.8% as measured by total recovery in all tissues and expiration
Details on distribution in tissues:
Carcass - 2.3%
Skin - 1.3%
Liver - 0.5%
Kidney - 0.1%
Blood - 0.1%
Brain - 0.02%
Fat - not detected
Details on excretion:
60% excreted via urine, and 27% via exhalation by 48 hours.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
* Sulfate conjugate
* Glucuronide conjugate
* Propylene glycol
* Dipropylene glycol and propylene glycol monomethyl ether (PM)
* DPM (2 isomers)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Radiolabelled DPM was readily excreted via urine and expired air following a single bolus oral dose. A number of metabolites were formed.
Executive summary:

Radiolabelled 14 -C DPM was administered by oral gavage to three male rats at a dose of 1289 mg/kg. Expired air and excreta were monitored for 48 hours for residues. DPM was well absorbed (93.8%) by gavage, and 87% was excreted via urine or expired air in the form of several main metabolites and sulfate and glucuronide conjugates by 48 hours.