Methylthiouracil

Basic toxicokinetics

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

The accumulation of 35S-antithyroid drugs by the thyroid gland

Author:

Marchant et al.

Year:

1972

Materials and methods

Objective of study:

other: accumulation in thyroid

Test guideline

Qualifier:

no guideline available

GLP compliance:

not specified

Test material

Radiolabelling:

yes

Remarks:

35-S

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Commercial diet 41B, iodine content 2ug/g, tap-water ad lib.

Administration / exposure

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

Doses / concentrations

Dose / conc.:

170 other: ug

No. of animals per sex per dose / concentration:

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.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

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

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

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

Applicant's summary and conclusion

Conclusions:

Methylthiouracil was shown to accumulate in thyroid gland.