Imidazolidine-2-thione

Endpoint summary

Description of key information

Toxicological data are available on ETU in the litterature.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

1

Additional information

Ethylene thiourea is absorbed by the gastrointestinal tract, the skin and most probably also through the respiratory tract. Data from animal experiments show that ethylene thiourea is rapidly absorbed from the digestive tract. Ethylene thiourea is limited distributed throughout the body and accumulates in the thyroid gland. There are species differences in the pattern of biotransformation. Ethylene thiourea is excreted primarily in the urine (up to 90%), but small quantities are excreted in the faeces and by exhalation. Ethylene thiourea 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.

Discussion on bioaccumulation potential result:

No data is available to indicate whether ETU can be absorbed via the lungs following inhalatory exposure. However, given its physical characteristics, such as its solubility in water, it is probable that ETU passes easily through the lung membranes.

Imidazoline, ethylene urea, 4-imidazolin-2-one(imidazolone) and unchanged ethylenethiourea were identified in the 24-h urine of male Sprague-Dawley rats after oral administration of 4 mg/kg bw [14C]ethylenethiourea. In two female cats given the same dose, a half-time of 3.5 h was determined, and ethylenethiourea, ethylene urea and S-methyl ethylenethiourea were present in the 24-h urine. S-Methyl ethylenethiourea comprised 64% of the total radiolabel in urine. Newsome (1974) found that approximately 60 and 44% was eliminated in the urine of rats and guinea pigs, respectively, and ca.1% in the faeces. In-vitro metabolism by cat and rat liver microsomes also produced ethylene urea, imidazoline and other unidentified compounds. When cat liver supernatant contained S-adenosyl methionine, S-methyl ethylenethiourea was produced (Iverson et al., 1980). The main metabolite of [14C]ethylenethiourea, formed in vivo after treatment of male NMRI mice with an oral dose of 67 mg/kg bw or in vitro with mouse liver microsomes, was 2-imidazolin-2-yl sulfenate (Savolainen & Pyysalo, 1979). A metabolite of ethylenethiourea detected in female rat plasma was identified as 1-methylthiourea (Kobayashi et al., 1982). After ethylenethiourea was administered once orally at 200 mg/kg bw to Wistar rats on day 12 of gestation, the concentration in maternal plasma and amniotic fluid peaked at about 2 h and disappeared within 48 h. In the embryos, the concentration peaked after only 30 min and disappeared within 48 h (Iwase et al., 1996). In pregnant Wistar rats given a single oral dose of 240 mg/kg bw [14C]ethylenethiourea, maternal blood maintained peak radiolabel concentrations for 2 h; the distribution was equal among maternal tissues but lower in embryos. Twenty-four hours after treatment, the radiolabel had been cleared and 72.8% had been excreted in the urine. The elution patterns suggested very little metabolism of the parent compound (Ruddick et al., 1975). When Wistar rats were given 100 mg/kg bw [14C]ethylenethiourea orally on day 12 of gestation, the compound was readily absorbed, the concentration reaching a maximum in maternal blood within 2 h. Ethylenethiourea was distributed throughout the maternal system and the embryo. Accumulation was noted in the thyroid. The major elimination route was the urine (Kato et al., 1976). Swiss mice and Wistar rats were treated by gavage on gestational day 15 with 240 mg/kg bw [14C]ethylenethiourea (mice) or [35S]ethylenethiourea (rats). The maternal and fetal concentrations of ethylenethiourea in tissues were similar in the two species 3 h after treatment, but the mice eliminated ethylenethiourea more rapidly, with a half-time of 5.5 h in mice and 9.4 h in rats (Ruddick et al., 1977). Two female rhesus monkeys (Macaca mulatta) and four Sprague-Dawley rats were given [14C]ethylenethiourea at 40 mg/kg bw by gastric intubation, and excretion was monitored for 48 h. The major excretion route was urine. The amount retained in tissues at 48 h was much higher in the two monkeys (21 and 28%) than in the rats (1%) (Allen et al., 1978).

Discussion on absorption rate:

A study with guinea pigs (Teschima 1981) showed that uptake of ETU through intact skin was relatively slow: 14% of 2-14C- ethylene thiourea (15 mg/ml, 1 ml applied to an area of 4 x 4 cm) was absorbed within 24 hours. If the skin was damaged, uptake within 24 hours was 42%.

Feldman and Maibach (1972, 1974) have shown that 0.88% of topical dose of thiourea penetrates human skin. According to the Criteria Documents from the Nordic Expert Group (Arbete och Hälsa, 1993:35), it is probably safe to use the same figure for the assessment of dermal exposure of ethylene thiourea in humans.