thiourea; thiocarbamide

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: case study; single patient

Data source

Reference

Reference Type:

publication

Title:

Thiourea causing granulopenia and thrombopenia.

Author:

Newcomb, P. B. and Deane, B. W.

Year:

1944

Bibliographic source:

Lancet 243 (6284):179

Materials and methods

Study type:

clinical case study

Endpoint addressed:

repeated dose toxicity: oral

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

oral application of thiourea as thyroid depressant

Test material

Test material information

Constituent 1

Reference substance name:

Thiourea

EC Number:

200-543-5

EC Name:

Thiourea

Cas Number:

62-56-6

Molecular formula:

CH4N2S

IUPAC Name:

thiourea

Test material form:

solid

Details on test material:

carbon atom in thiourea was radiolabelled

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 1
- Sex: female
- Age: 44
- Known diseases: admitted to hospital complaining of nervousness, sweating, palpitations and hot flushes which had' been getting worse for the last year. She had been given medicine for " thyroid trouble " 3 years before;
moderately severe degree of thyrotoxicosis, with the nervous elements more in evidence than the cardiovascular signs; very emotional; skin was flushed and moist; pulse-rate 100 per min; well-marked bilateral exophthalmos with some conjunctival injection; diffuse enlargement of the thyroid which was smooth and firm
Other: Treatment was started with a phenobarbitone and bromide mixture for a week, and during this time the pulse rate varied between 100 and 84 per min.

Ethical approval:

not applicable

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

1. Dosage: 1 gramme (3x per day) for 3 weeks. During this time teh patient remained well apart from a mild attack of influenza which was then epidemic. The fever lasted for 4 days.
About 10 days after thiourea had been started the signs of hyperthyroidism began gradually to improve (patient became less emotional and the pulse settled to a constant rate of about 80 a minute.
2. Dosage: 1 g. (twice a day) for 1 week
3. Dosage: 1 g. daily, during which time the improvement was maintained although it was not as great as might have been expected fromiodine.

Results and discussion

Clinical signs:

A fortnight after the drug had been started a leucocyte.count 'showed a total of 9200 with 70% granulocytes and a normal differential count.
After a total of 83 g. had been given-i.e., after 5 weeks treatment with thiourea—the patient suddenly had two epistaxes and then developed generalised purpura and ecchymoses with purpuric spots on the buccal mucous membrane which ruptured leaving painful ulcers. The spleen was not palpable.
Thiourea was immediately stopped and next day the ecchymoses had become more numerous and there was bleeding from the gums. A blood-count at this time showed red cells 4,500,000 per c.mm.; Hb. 87%; white cells4100 perc.mm. with 24% granulocytes. The platelet count was 18,000. Bleeding time was greatly prolonged and even at the end of 4 hours the bleeding from the puncture wound showed no signs of stopping. Coagulation-time was normal. Sternal puncture showed a marrow which was quite cellular ; the differential count showed 7% polymorphs, 16% lymphocytes, 44% myelocytes, 10.5% myeloblasts; there were 39% erythroblasts and 48% normoblasts. Platelets were scanty and 2 megakaryocytes were seen. Since many myelocytes were present the prognosis was thought to be good. By the second day after the purpura was first observed the leucocytes had fallen to 3700 per c.mm. with 16% polymorphs, and there were only 9000 platelets. The patient was therefore transfused with a pint of fresh whole blood and all bleeding from the gums ceased 10 minutes after the transfusion had started. Pentnucleotide, 10 c.cm. (twice daily), was also started but was discontinued after six doses because it caused some pyrexia.
Subsequent blood-counts have shown a gradual return to normal, and the latest count taken 12 days after the appearance of the purpura showed a leucocyte-count of 6200 per c.mm. with 36% granulocytes, and 67,000 platelets per c.mm. The purpura and ecchymoses have faded and there has been no further hremorrhage.
During the time this patient was in hospital no other drugs were given and it seems fairly certain that the toxic effects were due to thiourea.

Any other information on results incl. tables

A female patient was treated for hyperthyroidism with 85g Thiourea for 5 weeks (1-3g/d; 20-60 mg/kg/d) without adverse effects. After 5 weeks significant side effects were reported (blood count, hemorrhage, granulocytopenia), which showed a gradual return to normal within 12 days.

Applicant's summary and conclusion

Conclusions:

A female patient was treated for hyperthyroidism with 85g Thiourea for 5 weeks (1-3g/d; 20-60 mg/kg/d) without adverse effects. After 5 weeks significant side effects were reported (blood count, hemorrhage, granulocytopenia), which showed a gradual return to normal within 12 days.

Executive summary:

A female patient was treated for hyperthyroidism with 85g Thiourea for 5 weeks (1-3g/d; 20-60 mg/kg/d) without adverse effects. After 5 weeks significant side effects were reported (blood count, hemorrhage, granulocytopenia), which showed a gradual return to normal within 12 days.