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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study with acetable limitations

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Dynamik von 15N-Isobutylidendiharnstoff (IBDH) bei Schafen.
Author:
Bergner H, Görsch R, Adam K
Year:
1978
Bibliographic source:
Arch. Tierernaehrung, 28(8): 575-583
Reference Type:
publication
Title:
Untersuchungen zum Umsatz von markiertem Isobuylidenhdiharnstoff beim Wiederkäuer.
Author:
Görsch R
Year:
1980
Bibliographic source:
Arch. Tierernährung: 30, 221-228

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
The distribution of 15N-labelled isobutyliden diurea in sheep was examined.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
no further data
Radiolabelling:
yes
Remarks:
15N-Isobutylidene diurea

Test animals

Species:
sheep
Strain:
other: Merino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 41.2, 42.4, 46.3, 50.2 and 52.6 kg

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
no further data
Duration and frequency of treatment / exposure:
no details given
Doses / concentrations
Remarks:
Doses / Concentrations:
60 g/d (ca. 1260 mg/kg bw) of Isobutylidene diurea ; no data available on the amount of radiolabelled 15N-Isobutylidene diurea administered
No. of animals per sex per dose:
5 male animals
Control animals:
not specified
Positive control:
no data
Details on study design:
The urine was collected from all animals, blood was collected from four animals at the timepoint of sacrifice, the other animal with a omasum-abomasum ligature had the blood collected 2.5, 7.25, 12 and 24 hours after dosing. The TCA-soluble and TCA-precipitable portions of blood plasma, urine and liver were analysed for 15N-content, the whole blood plasma for NH3, urea and IBDU, and urine for these 3 compounds in labelled and unlabelled form, respectively. From another wether provided with a ligature at the abomasus entry and killed 24 hours after isotope intake, the same analyses were taken.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, blood, plasma, liver
- Time and frequency of sampling: blood: 2.5, 7.25, 12 and 24 hours after dosing

Results and discussion

Any other information on results incl. tables

Whilst all four sheep revealed an almost equal urea level ranging from 18 to 30 mg per 100 ml blood plasma, IBDU was only detectable in the animal killed 12 hours after the start of the experiment, amounting to 17.3 mg/100 ml blood plasma (ca. 2.2 % of the last IBDU - intake). The blood plasma of the wether with ligature was found to contain up to 18.2 mg IBDU/100 ml and up to 98.7 mg urea per 100 ml blood plasma. This finding is regarded as evidence of the possibility of IBDU to be absorbed through the rumen wall. The 15N-IBDU was incorporated into the blood plasma proteins. In the urine, only low amounts of unchanged IBDU (max. 1 % of intake) were recovered within 24 hours. Max. 4 % of  15N-intake were recovered in the livers (7.25 h sacrifice). After 24 h, about 50% of the applied 15N were still present in the rumen.  However, it was not determined whether this was due to 15N-IBDU, or from labelled proteins or urea. The passing of nitrogen from IBDU into the body pool was assumed from the results of recovery experiments which demonstrated the presence of 15N in plasma proteins and liver.

Applicant's summary and conclusion