1-[(2-hydroxyethyl)thio]propan-2-ol

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: expert assessment

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment of the toxicokinetics behaviour of the substance was performed using results fr om existing toxicological studies and information from an analogue substance.

Objective of study:

toxicokinetics

Qualifier:

no guideline required

Principles of method if other than guideline:

An assessment of the toxicokinetics behaviour of the substance was performed using results from existing toxicological studies and information from an analogue substance.

GLP compliance:

no

Type:

absorption

Results:

Adsorption via the oral and dermal routes is expected but was not confirmed by experimental data.

Details on absorption:

Oral Exposure:
1-[(2-hydroxyethyl)thio]propan-2-ol is a water soluble organic substance with a low molecular weight (136.21 g/mol) therefore absorption in the gastrointestinal tract is likely (ECHA, 2017).
The pKa of 1-[(2-hydroxyethyl)thio]propan-2-ol is ~15 therefore the substance will not be ionised in the range of the pH considered relevant to the human body (pH 2-9). This lack of ionisation is expected to enable the diffusion of the substance across biological membranes (ECHA, 2017).
A Log Kow of -0.2 was predicted for 1-[(2-hydroxyethyl)thio]propan-2-ol using a QSAR model. This value is between -1 and 4 and therefore supports the fact that the substance is likely to be absorbed following oral exposure (ECHA, 2017).
A short-term repeated-dose toxicity study via the oral route was performed on 1-[(2-hydroxyethyl)thio]propan-2-ol according to a method similar to the OECD Testing Guideline 407. The study was GLP-compliant and was attributed a Klimisch score of 2 (reliable with restrictions). Exposure for 28 days at up to 1,000 mg/kg bw/d did not allow observation of treatment-related effects in animals at the end of the study when compared to controls. It is not possible to determine if this absence of treatment-related effects is due to the lack of toxicity of the test substance at the concentrations investigated, or if it resulted from a lack of absorption following oral exposure.
No additional data has been identified which investigates the effects of 1-[(2-hydroxyethyl)thio]propan-2-ol following exposure via the oral route. Therefore, it is not possible to confirm if 1-[(2-hydroxyethyl)thio]propan-2-ol is absorbed following an exposure via the oral route as expected.

Inhalation Exposure:
1-[(2-hydroxyethyl)thio]propan-2-ol has a vapour pressure of 1.13 mmHg (150.654 Pa) and a boiling point of 270°C at 101.325 kPa. Therefore it is not expected to be available for inhalation as a vapour (ECHA, 2017).
No data has been identified in the literature investigating the effects of 1-[(2-hydroxyethyl)thio]propan-2-ol following exposure via inhalation.

Dermal Exposure:
Since the substance has a molecular mass of 136.21 Da, it could theoretically be absorbed following dermal exposure (Bos et al, 2000). However the dermal absorption of 1-[(2-hydroxyethyl)thio]propan-2-ol would be limited by the hydrophilic nature of the substance (ECHA, 2017).
No data has been identified in the literature investigating the effects of 1-[(2-hydroxyethyl)thio]propan-2-ol following an exposure via the dermal route. Therefore, it is not possible to determine if 1-[(2-hydroxyethyl)thio]propan-2-ol is absorbed following exposure via the dermal route.
1-[(2-hydroxyethyl)thio]propan-2-ol was found not to be an irritant or corrosive to the skin, therefore it is not expected to damage the skin or enhance dermal absorption.
Reifenrath et al. (2002) investigated the dermal absorption of the analogue substance thiodiglycol. A percutaneous absorption of 20% was determined. Due to the similarities between 1-[(2-hydroxyethyl)thio]propan-2-ol and thiodiglycol, specifically their molecular weight and structure, a similar dermal absorption can be expected from 1-[(2-hydroxyethyl)thio]propan-2-ol.

Details on distribution in tissues:

Since 1-[(2-hydroxyethyl)thio]propan-2-ol is a hydrophilic substance with a low molecular weight, it is expected to be well-distributed in a mammalian body through the water compartments but is not expected to accumulate in tissues (ECHA, 2017).
One animal study was identified on the substance. No treatment-related effects were observed during this study, therefore it does not allow extraction of information on the distribution of 1-[(2-hydroxyethyl)thio]propan-2-ol.

Details on excretion:

No data on the excretion of 1-[(2-hydroxyethyl)thio]propan-2-ol were identified.
Black et al. (1993) determined that the analogue substance thiodiglycol and its metabolites were eliminated mainly via the urine (between 93% and 99%) following an intraperitoneal injection of thiodiglycol. No significant excretion was identified in the faeces. Taking into account the structural similarities between 1-[(2-hydroxyethyl)thio]propan-2-ol and thiodiglycol, it is expected that urine is the main route of excretion for absorbed 1-[(2-hydroxyethyl)thio]propan-2-ol.
Elimination of 1-[(2-hydroxyethyl)thio]propan-2-ol via urine is consistent with the low molecular weight (below 300 g/mol) and high water solubility of the substance (ECHA, 2017).

Metabolites identified:

no

Details on metabolites:

No data on the metabolisation of 1-[(2-hydroxyethyl)thio]propan-2-ol were found.
Due their structural similarities, it is expected that 1-[(2-hydroxyethyl)thio]propan-2-ol and its analogue thiodiglycol undergo a similar metabolisation process. Thiodiglycol is metabolised mainly to thiodiglycol sulfoxide, with S-(2-hydroxyethylthio)acetic acid, thiodiglycol sulphone and S-(2-hydroxyethylsulfinyl)acetic acid as minor metabolites (Black et al., 1993). Therefore absorbed 1-[(2-hydroxyethyl)thio]propan-2-ol is expected to undergo a similar metabolisation process to produce 1-[(2-hydroxyethyl)thio]propan-2-ol sulfoxide, S-(2-hydroxypropylthio)acetic acid, 1-[(2-hydroxyethyl)thio]propan-2-ol sulphone and S-(2-hydroxypropylsulfinyl)acetic acid.

Conclusions:

An assessment of the toxicokinetics behaviour of the substance was performed using results from existing toxicological studies and information from an analogue substance.

Executive summary:

The absence of specific toxicokinetic data from animal testing means that it is not possible to make firm conclusions concerning the absorption, distribution, metabolisation and excretion of 1-[(2-hydroxyethyl)thio]propan-2-ol. However, it was possible to use existing data on the physical, chemical and toxicological properties of the substance, as well as data available for the analogue thiodiglycol, to determine the likely toxicokinetic behaviour of 1-[(2-hydroxyethyl)thio]propan-2-ol.

 

1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be well-absorbed following exposure via the oral route, considering its low molecular weight, high water solubility, and predicted Log K_ow of -0.20. Available animal data on the substance do not allow confirmation that absorption occurs following oral exposure. 1-[(2-hydroxyethyl)thio]propan-2-ol is not expected to be available as a vapour due to its low vapour pressure and therefore no absorption via inhalation is expected. Absorption via the dermal route cannot be excluded, taking into account the substance’s low molecular mass and data on the analogue substance thiodiglycol, however, dermal absorption is expected to be limited by the hydrophilic nature of the substance.

 

1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be well-distributed in the human body due to its low molecular weight and high water solubility but it is not expected to accumulate. Available animal data on the substance do not provide evidence to support this prediction.

 

No data is available on the metabolisation and excretion of 1-[(2-hydroxyethyl)thio]propan-2-ol. However the substance is expected to undergo a process similar to the substance thiodiglycol due to their structural similarities. Therefore1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be metabolised to 1-[(2-hydroxyethyl)thio]propan-2-ol sulfoxide, S-(2-hydroxypropylthio)acetic acid, 1-[(2-hydroxyethyl)thio]propan-2-ol sulphone and S-(2-hydroxypropylsulfinyl)acetic acid. Eventually, the unchanged, absorbed compound and its metabolites are expected to be eliminated via the urine.

 

It is not considered justified to perform animal studies on this substance to further investigate its toxicokinetics behaviour.

Description of key information

The absence of specific toxicokinetic data from animal testing means that it is not possible to make firm conclusions concerning the absorption, distribution, metabolisation and excretion of 1-[(2-hydroxyethyl)thio]propan-2-ol. However, it was possible to use existing data on the physical, chemical and toxicological properties of the substance, as well as data available for an analogue, to determine the likely toxicokinetic behaviour of 1-[(2-hydroxyethyl)thio]propan-2-ol.

 

1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be well-absorbed following exposure via the oral route, considering its low molecular weight, high water solubility, and predicted Log K_owof -0.20. Available animal data on the substance do not allow confirmation that absorption occurs following oral exposure. 1-[(2-hydroxyethyl)thio]propan-2-ol is not expected to be available as a vapour due to its low vapour pressure and therefore no absorption via inhalation is expected. Absorption via the dermal route cannot be excluded, taking into account the substance’s low molecular mass and data on the analogue substance, however, dermal absorption is expected to be limited by the hydrophilic nature of the substance.

 

1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be well-distributed in the human body due to its low molecular weight and high water solubility but it is not expected to accumulate. Available animal data on the substance do not provide evidence to support this prediction.

 

No data is available on the metabolisation and excretion of 1-[(2-hydroxyethyl)thio]propan-2-ol. However the substance is expected to undergo a process similar to the substance thiodiglycol due to their structural similarities. Therefore1-[(2-hydroxyethyl)thio]propan-2-ol is expected to be metabolised to 1-[(2-hydroxyethyl)thio]propan-2-ol sulfoxide, S-(2-hydroxypropylthio)acetic acid, 1-[(2-hydroxyethyl)thio]propan-2-ol sulphone and S-(2-hydroxypropylsulfinyl)acetic acid. Eventually, the unchanged, absorbed compound and its metabolites are expected to be eliminated via the urine.

 

It is not considered justified to perform animal studies on this substance to further investigate its toxicokinetics behaviour.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential