1,3,4-Thiadiazolidine-2,5-dithione, reaction products with tert-dodecanethiol and hydrogen peroxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

An extensive assessment of the toxicological behaviour of 1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol was performed, taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

no guideline required

Test material

Test material information

Constituent 1

Reference substance name:

5-[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole-2-thiol; bis[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole

EC Number:

939-692-2

Cas Number:

1474044-73-9

Molecular formula:

not applicable (UVCB substance)

IUPAC Name:

5-[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole-2-thiol; bis[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole

Administration / exposure

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Based on physico-chemical properties which are not suggestive for a significant absorption (insoluble in water, high LogPow, MW>500 and low vapour pressure), absorption of the substance into the body is expected to be low via all exposure routes.

Main ADME results 2

Type:

distribution

Results:

The distribution is expected to be limited due to low absorption.

Main ADME results 3

Type:

excretion

Results:

Concerning the fates of metabolites formed, they are expected to be eliminated via the urine.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

For the target substance, even though the very high LogPow would indicate the possibility to reach the intracellular compartment, this seems to be unlikely as the molecular weight of the unmetabolised substance is rather high and the absorption of unchanged substance is considered to be very limited. Therefore, the distribution is also expected to be limited.

Details on excretion:

For the target substance no data is available concerning its elimination. Concerning the fate of the metabolites formed, the metabolites should be eliminated mainly via the urine.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

If absorbed, the substance is expected to be metabolised by Phase I drugs metabolising enzymes with followed conjugation by Phase II reactions. Thioester derivatives and hydroxylated derivatives at C atoms of the hydrocarbon chain are primary metabolites expected.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results
An extensive assessment of the toxicological behaviour of 1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol was performed (expert statement), taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Executive summary:

In order to assess the toxicological behaviour of 1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol, the available physico-chemical and toxicological data have been evaluated. The substance is expected to be absorbed to a limited extent after oral exposure, based on its rather high molecular weight (551 g/mol, which is above the upper limit favourable for absorption), its low water solubility and its high LogPow. Concerning the absorption after exposure via inhalation, as the chemical is considered to have a fairly low vapour pressure, is highly lipophilic, has a high LogPow, and has a rather high molecular weight, it is clear, that the substance is poorly available for inhalation and will not be absorbed significantly. The substance is also not expected to be absorbed following dermal exposure into the epidermis, due to its low water solubility and its fairly high molecular weight. Concerning its distribution throughout the body, the target substanceis not expected to be distributed extensively due to the low absorption. If absorbed, it is likely to distribute into the both intravasal and intracellular compartments.

The substance does indicate a significant potential for accumulation based on the high logPow (8; logPow of 9.4 was identified for the read-across substance), this, however, is limited as the absorption is expected to be low via all routes of exposure. Moreover,metabolism of the substance is expected to influence this initial prediction. The substance is expected to hydrolyse under neutral conditions (i.e. small intestines) and be extensively metabolisedby cytochrome P450 enzymes, by omega- and beta-oxidation, via S-oxidation, metabolic reduction, desulfonation and possibly deamination andN-acetylation andto be eliminated mainly via the urine.