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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

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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: Study well documented, acceptable for assessment, draft report

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1985
Reference Type:
secondary source
Title:
Unnamed
Year:
1985

Materials and methods

Objective of study:
other: Adsorption, Disposition, Metabolism and Excretion
GLP compliance:
not specified

Test material

Constituent 1
Details on test material:
- Radiochemical purity (if radiolabelling): > 90%
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeders (Kingston, NY)
- Weight at study initiation: 240 - 347 g
- Housing: individual
- Individual metabolism cages: yes
- Diet: Certified Purina Rat Chow
- Water: furnished water
- Acclimation period: at least 1 week

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses / concentrations
Remarks:
Doses / Concentrations:
502, 979 and 1970 mg 14C-TS per kg b.w.
No. of animals per sex per dose / concentration:
4
Control animals:
no
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, liver, blood, entire small tissues, and portions of muscle, skin and adipose tissues
-Time and frequency of sampling: 0-0.5, 0.5-2, 0-6, 6-12, 12-24, 24-36, 36-48, 48-72 h
- From how many animals: (samples not pooled) 4
- Method type(s) for identification: total radioactivity was analysed by scintillation spectrophotometer, TS by HPLC

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Oral absorption of DMDHEU, based on urinary excretion, increased with increasing dosed amounts. An average of 17% of the 502 mg/kg dose was absorbed, 28% of the 979 mg/kg dose and 38% of the 1970 mg/kg dose. The reason for this increase in oral absorption with increasing dose level is not clear (statement by the author) .
Details on distribution in tissues:
Concentrations of radiolabeled compounds in tissues, in general, reflect the increased systemic load of [14C]DMHEU as the dose increased from 502 mg/kg (85 mg/kg absorbed) to 979 mg/kg (274 mg/kg absorbed) to 1970 mg/kg (749 mg/kg absorbed).
Details on excretion:
Orally administered DMDHEU was excreted both in urine and in feces. More than 90% of the 14C that was excreted in urine was excreted within 24 h after dosing.
Distribution of the 14C in tissues following oral dosing was similar to that found after intravenous dosing, where one-half hour after an intravenous dose of 51 mg/kg of [14C]DMDHE , an average of 26 % of the dose was recovered from the bladder contents and tissues containing significant fractions of the dose were skin (13%), muscle (12%), blood (6 %), liver (6%) and kidney (5 % ). Two hours after i.v. administration the percent dose in these tissues had decreased by factors of 4-12. Two tissues had tissue-blood ratios significantly greater than 1 at this time point - prostate (TBR=11) and seminal vesicle (TBR=5). By 72 h after i.v. dosing, less than 0 .5% of the dose remained in the tissues. Most of this (0 .3%) was found in muscle. Approximately 6 times as much 14C was present in blood at 72 h as was in plasma alone. A number of other tissues showed tissue-blood ratios greater than 1. This suggests that a very small portion of the DMDHEU may be metabolized to a relatively long lasting metabolite which may be covalently linked to biomolecules. (Tissue data for oral application not readable).

Applicant's summary and conclusion