Ethylene thiourea: Health-based recommended occupational exposure limit

Scope

At the request of the Minister of Social Affairs and Employment, the Health Council of the Netherlands recommends health-based occupational exposure limits for the concentrations of toxic substances in air at the workplace. These recommendations are made by the Council’s Dutch Expert Committee on Occupational Standards (DECOS). They constitute the first step in a three-step procedure that leads to legally binding limit values.

In the present report, the committee discusses the consequences of occupational exposure to ethylene thiourea (ETU) and recommends a health-based occupational exposure limit. The committee’s conclusions are based on scientific publications prior to 1995.

Physical and chemical properties

ETU is an odourless, white to light green crystalline powder at room temperature. ETU is a fairly stable compound in terms of hydrolitic activity, but is easily oxidized to ethylene urea (EU). ETU is explosive when finely dispersed in air; the compound is flammable. ETU is amongst others used as an intermediate for antioxidants and in the manufacture of synthetic resins.

Monitoring

The accepted method of determining atmospheric ETU concentrations at the workplace is described in the NIOSH Manual of Analytical Methods; it is based on use of a spectrophotometer at 590 nm. The detection limit is 0.0075 mg/m3 in a hundred-litre sample for 0.01 absorbance, using five-centimetre optical path length cells.

Current limits

No occupational exposure limits have been set in the Netherlands, the United States, Germany or the United Kingdom.

Toxicokinetics

ETU is absorbed by the gastrointestinal tract, the skin and most probably also through the respiratory tract. No quantitative data on uptake through these organs is available. ETU is limited distributed throughout the body and accumulates in the thyroid gland. There are species differences in the pattern of biotransformation. ETU is excreted primarily in the urine (up to 90%), but small quantities are excreted in the faeces and by exhalation. ETU and its metabolites have a half-life of about twenty-eight hours in monkeys, nine to ten hours in rats and five hours in mice. Biological monitoring has been performed by determining ETU concentrations in the urine. In humans, the estimated half-life for elimination of ETU through the kidneys is about one hundred hours.

Effects

ETU is slightly irritating to the skin. Acute toxicity studies indicated that rats are more susceptible to ETU than mice. Short-term toxicity studies demonstrated that the thyroid gland is the most affected organ. Reduced T3_ and T4_ secretion and increased TSH (thyroid-stimulating hormone) secretion are found in rats. There are also qualitative differences between rats and mice in terms of their hepatic xenobiotic metabolizing systems. ETU may induce ultrastructural changes in the proximal tubuli of the rat kidneys. The compound may also cause aberrations of the peripheral nervous system of rats.

ETU is carcinogenic to rats, inducing thyroid cancer. In mice, it induces liver adenomas and carcinomas. However, ETU has not been found to be carcinogenic to hamsters and it is not mutagenic. The committee endorses the European Union’s conclusion that the carcinogenicity of ETU to rodents is not relevant for assessing risks of human occupational exposure. The effects observed appear to be related to characteristics of rodent thyroid gland physiology.

ETU is teratogenic in rats. The foetal organs which are most affected are the central nervous system, the kidneys, the ureter and the skeleton.
Limited human data are available. From a cross-sectional study, it has been demonstrated that occupational exposure to ETU induces aberrations in the functioning of the thyroid gland, e.g. reduced thyroxine levels in the serum. There is no conclusive human evidence that ETU causes allergic contact dermatitis.

Hazard assessment and recommended exposure limit

The committee is of the opinion that a health-based recommended occupational exposure limit for ETU should be based on the results of the human cross-sectional and follow-up study of workers occupationally exposed to ETU. From this study the committee concludes that after exposure to an ETU concentration of 0.120 mg/m3, the T4 levels in serum are significantly reduced. Taking this concentration as the lowest observed adverse effect level (LOAEL) and applying a safety factor of 5, the committee recommends an health based occupational exposure limit for ETU of 0.024 mg/m3 as an 8-hour time weighted average concentration.

Committee