Thiourea synthesis by thioacylation

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Consumer exposure to thiourea can occur from the metabolism of thiourea-based pharmaceuticals.

The iodine level of the thyroid gland was reduced from 73 to 13 mg/100 g tissue upon the oral administration of thiourea at 70 mg/kg body weight for 10 days (Astwood et al., 1945). Thiourea also resulted in a reduction of thyroid iodine uptake when administered in rats at 1% (500 mg/kg body weight per day) in the diet for 2 months (Keston et al., 1944). Concomitant with reduced thyroid activity, the weight of the pituitary gland increased and signs of pituitary overactivity were evident both histologically and biochemically; the weights of the ovary, uterus, and prostate gland all declined. Haemosiderosis in the spleen, lymph nodes, and intestinal villi of rats was observed subsequent to the administration of 16–50 daily doses of 1 ml of a 1% aqueous solution of thiourea by gavage. The repeated administration of high doses (no quantitative data given) of thiourea in the diet, in the drinking-water, or by intraperitoneal injection resulted in manifold effects: reduced osmotic resistance of the erythrocytes, congestion, haemosiderosis and atrophy of the spleen, anaemia, leukocytopenia, granulocytopenia, increased erythropoiesis in the bone marrow, reduced clotting times, and increased phospholipid levels of the blood (MAK, 1988).

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When 28-day-old male rats (strain not given) were treated daily for 2 weeks with thiourea administered at 600 ± 60 mg/kg body weight via gastric intubation, about a 50% reduction of body weight gain was observed (Smith, 1950). Daily ingestion of 131 mg thiourea/kg body weight in drinking-water by 21- to 30-day-old female rats (strain not given) for 10 consecutive days led to hyperplasia of the thyroid, which could be demonstrated both macroscopically and microscopically. No such effect resulted from treatment with 12 mg thiourea/kg body weight (Astwood, 1943). Another study demonstrated a reduction of the basal metabolic rate, which could be prevented by simultaneous administration of thyroxine (tetraiodothyronine, or T4) (MacKenzie & MacKenzie, 1943). Rats received, over a 2-week period, 0.05% thiourea (25 mg/kg body weight per day) up to 2% thiourea (1000 mg/kg body weight per day) in food. The weight of the thyroid glands was increased maximally in rats that received 0.5% thiourea (250 mg/kg body weight per day); the basal metabolic rate showed a definite depression in rats receiving 1% thiourea (500 mg/kg body weight per day). The basal metabolic rate was determined in rats that were starved for 20 h (no further details are given).

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In all of the vulcanization accelerators, pharmaceuticals, and pesticides being synthesized from thiourea, the basic structure of the substance is maintained. It is therefore possible that thiourea can be released from these agents by metabolic or hydrolytic degradation. However, a quantification of the thiourea releases into the environment is not possible with the available data.

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Rheinheimer et al. (1990) investigated the aerobic biodegradability of environmentally relevant concentrations of organic chemicals (including, among others, thiourea) in water and sediment samples of the river Elbe (including its estuary) and the western reaches of the Baltic Sea. In all water samples from the Elbe estuary, very slow but continuous degradation of thiourea was observed over the incubation period of 85 days (maximum 9% within the first 8 days, maximum 68% at the end of observation; based on carbon dioxide production). In sediment samples, 40–70% degradation was observed. In samples taken from the Baltic Sea, biodegradation varied widely between 50 and 87% in water and between 28 and 72% in sediment.

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From the available degradation tests and taking into account the expected environmental distribution of thiourea, leaching of this compound from soil to ground-water seems possible, particularly under conditions unfavourable for biotic degradation.

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The use of thiourea in metal polish occurs in industrial and consumer products as well. From this type of application (aqueous solutions), it can be assumed, as a worst case, that the total amount used is released into wastewater. In Germany, this is about 13.2 tonnes/year.