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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Reference:
Composition 0
Objective of study:
other: accumulation in thyroid
Qualifier:
no guideline available
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
35-S
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Commercial diet 41B, iodine content 2ug/g, tap-water ad lib.
Route of administration:
oral: drinking water
Vehicle:
other: alkaline saline (pH 8.0)
Details on exposure:
Methylthiouracil was adminístered in 0.2 ml alkaline saline
Duration and frequency of treatment / exposure:
After 8 hr all animals were killed
Dose / conc.:
170 other: ug
No. of animals per sex per dose:
Four
Control animals:
no
Details on study design:
35S labelled antithyroid drugs were administered in 1.2 umoles to normal rats. Thin-layer chromatography of the solutions immediately before injection demonstrated no significant breakdown. All animals were killed 8 hours afterinjection and the blood obtained by cardiac puncture into a heparinized syringe while under light ether anasthesia. The thyroids were quickly removed, dissected free of fat, weighed (wet weight) on a toriosn balance and homogenized in 0.5 ml of ice-cold distilled water in pyrex ground glass homogenizers. 0.1 ml of plasma and thyroid homogenates were transferred into liquid scintillation vials and analyzed with a scintillator. Aliquits of thyroid homogenates and plasma were analyzed using thin-layer chromatography and radiochromatogram.
Details on distribution in tissues:
Methylthiouracil is accumulated in thyroid gland. Thyroid:plasma ratio is 8.2 after 8 hours after substance administration.
Metabolites identified:
not measured

Table 1. Thyroid accumulation of 35S-labelled methylthiouracil to rats.

 Drug  Dose (ug)     Total 35S activity/g thyroid or ml plasma  

 Actual drug or

sulphate nmoles

/thyroid

     

35S - Methylthiouracil

nmoles/g thyroid nmoles/g plasma   Thyroid plasma 35S ratio  Sulphate Drug 

Plasma drug level

nmoles/ml

Drug thyroid:plasma

ratio

   170  66.1±6.3  1.63±0.18  43.1±5.6  14,5±2.2  9.9±0.9  1.2  8.2
Conclusions:
Methylthiouracil was shown to accumulate in thyroid gland.

Description of key information

Methylthiouracil was accumulated in thyroid gland. Thyroid:plasma ratio was 8.2 after 8 hours after substance administration.

Key value for chemical safety assessment

Bioaccumulation potential:
high bioaccumulation potential

Additional information

Methylthiouracil is a thionamide anti-thyroid drug, which has been used in the treatment of hyperthyroidism.