Tetrahydrothiophene

Endpoint summary

Description of key information

The data available on tetrahydrothiophene and the estimations from its physico-chemical properties indicate a significant absorption by inhalation exposure, a very low rate of dermal absorption, widespread distribution, rapid metabolism by oxidation of the sulphide functions and no bioaccumulation potential of parent and transformation products.

The absorption/excretion, toxicokinetics, metabolism and distribution data of tetrahydrothiophene were evaluated from the available toxicological data and the physicochemical properties as suggested by the REACH Guidance Chapter R.7c:

Molecular weight: 88.17 g/mol

Water solubility: 5800 mg/L

Partition coefficient log Kow = 1.8

Vapor pressure : 2400 Pa @25°C

ABSORPTION

Inhalation route

According to the REACH Guidance, the physicochemical characteristics of tetrahydrothiophene (log Pow 1.8) and the molecular mass (88.17 g/mol) are in a range suggestive of absorption as such from the respiratory subsequent to inhalation exposure. This assumption of absorption is confirmed by the mortality and clinical signs observed in the acute inhalation toxicity study (Terril, 1986). Therefore, a default inhalation absorption rate of 50% will be used for risk assessment.

Dermal absorption

The rate of absorption of tetrahydrothiophene was estimated using the IH SkinPerm model using a Kp derived from the EPI Dermwin model. The fraction of dose absorbed was 0.00383% for an instantaneous deposition and 0.00747% for a deposition over time. Therefore, a default skin absorption rate of 1% will be used for tetrahydrothiophene.

DISTRIBUTION and METABOLISM

According to the REACH Guidance, as a small molecule a wide distribution of tetrahydrothiophene propane is expected.

According to the limited information available, the metabolism of tetrahydrothiophene involves extensive oxidation. Tetrahydrothiophene-1,1-dioxide is formed from the sulfide, and this is then further metabolized to 3-hydroxytetrahydrothiophene-1,1-dioxide. Up to 85% of the ip administered dose is excreted in the urine within 24 hours (Roberts and Warwick, 1961).

In another limited study, two mice were each given a single intraperitoneal injection of 200 µl of a 0.9% sodium chloride solution containing 25 µCi [methyl-3H] methionine plus 25 mM tetrahydrothiophene, equivalent to 250 µmol/kg body weight (ca. 22 mg/kg body weight). In 1 mouse, 17.7 x 10e-3 cpm methyl sulfonium derivatives/g were found in the liver, while the corresponding figures for the lungs and the kidneys were 3.0 and 6.0 x 10e-3 cpm/g, respectively. The other mouse was kept in a metabolism cage. The 24-hour urine contained 19.3 x 10e-3 cpm/ml. The authors thus considered that in vivo, tetrahydrothiophene was metabolized to methyl sulfonium derivatives, which were then excreted in the urine (Mozier and Hoffman, 1990).

ELIMINATION

According to the REACH Guidance, the n-Octanol/water partition coefficient (log Pow of 1.83) and the metabolism is not suggestive of accumulation of unchanged tetrahydrothiophene in fatty tissues subsequent to absorption. Therefore, no potential for bioaccumulation is to be expected for tetrahydrothiophene.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

50