thiourea; thiocarbamide

Endpoint summary

Description of key information

Several pre-GLP/pre-OECD publications are available for the evaluating the toxicokinetics of Thiourea. In humans and animals, Thiourea is rapidly absorbed from the gastrointestinal tract (Williams, 1947). Three studies on dermal absorption show that Thiourea penetrates through the skin (Kosova, 1970; TNO 1979&1980). Slanina et al. (1973) examined the distribution of thiourea in mice (mother and fetuses); Hollinger examined the distribution in lung, liver and kidney. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

4

Additional information

Thiourea is rapidly absorbed from the gastrointestinal tract and excreted in the urine in humans and rats. A single oral dose of 28.57 mg/kg bw of Thiourea was almost completely eliminated from the blood within 48h in humans (Williams, 1947). In rats a recovery in the carcasses of 30% was reported 3h after intravenous injection of 5 mg thiourea - after 25h only traces were detected (Williams, 1947). The plasma half-time was determined with 3.3 h (Giri, 1972).

Hollinger (1974) reported distribution of Thiourea to lung, liver and kidney, with the highest proportion measured in lung tissue. Slanina (1973) reported accumulation of 14C-Thiourea in the thyroid gland of mother and fetusses in mice, showing that thiourea readily passes the blood-placenta barrier. Kosova (1970) applied thiourea to the skin of rats; it was considered to penetrate "easily". The amount was not quantified but estimated by systemic effects. 3,76 % of the amount dermal administered to rabbits was excreted in the urine after 24h (Leegwater, 1979). Vignole (1958) demonstrated that 50 -80% of orally or subcutaneous administered Thiourea is excreted unchanged in the urine by the rabbit within 3 days. According to Leegwater (1979, 1980) administration of aqueous solution facilitates the percutaneous absorption. The amount of Thiourea excreted in urine was between 3 and 4 % when administered as aqueous solution and only 0.1% when administered as dry powder.

Thiourea inhibits the thyroid hormone synthesis (Takegawa, 1997). Results of in vitro and in vivo studies showed that Thiourea is an inhibitor of thyroid peroxidase (1979). Thiourea is oxidized by the thyroid gland peroxidase forming cyanamide and elementary sulfur. In vitro, cyanamide inhibits the peroxidation of iodide and the iodination of tyrosine. This explains the thyroid depressant action of Thiourea. Autoradiographic studies of the distribution of 35S-labelled thiourea revealed a highly preferential and prolonged storage of the radioactivity in the thyroid gland [Schulman 1950]. Together with the main product, sulfate, protein-bound sulfur was detected [Maloof 1957]. The biochemical mechanisms of action of Thiourea can be summarized as follows: in addition to reductive activation which leads to breaking of disulfide bonds in protein, oxidation in the presence of iodine or with the flavoprotein-dependent aminoxidase is of importance. At least three mechanisms which depend on metabolism may contribute to toxicity – a) denaturation of functionally important proteins by breaking of disulfide bonds, forming thiosulfenic acids; b) membrane damage as a result of reduction in the GSH level in the lung, and c) metabolism to toxic sulfinic and sulfonic acids (MAK 1990).