Bis(piperidinothiocarbonyl) hexasulphide

Endpoint summary

Description of key information

No experimental toxicokinetic study is available on DPTH.

However, as per REACH guidance document R7.C , information on absorption, distribution, metabolism and excretion may be deduced from the physical-chemical properties and QSAR predictions.

Based on the physical-chemical properties and QSAR predictions, the absorption of DPTH is expected to be high by oral route and inhalation, but low by dermal route. A good distribution in the body and an excretion in bile and feces are expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

According to the REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physical-chemical properties, including:  

-Molecular weight: 448.82 g/mol

-Water solubility: 10.48 µg/L (20°C), DPTH is insoluble in water.

-Partition coefficient Log Kow: 4.43

-Vapour pressure: 0.00001 Pa (25°C)

 

ABSORPTION

The high value of log Kow (>4) and the low solubility (<100 mg/L) of DPTH are favorable for a low oral absorption. Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption of DPTH were 100 and 90% for a dose of 1 and 1000 mg, respectively (Danish QSAR). According to the model "Intestinal absorption (human)", 80% of the substance is absorbed (pkCSM).

No clinical effects or mortality were observed after one single administration (2000 mg/kg) of DPTH by gavage (oral route) in rat.

100% of oral absorption is taken into account for the risk assessment.

With a very low solubility,dermal absorption is anticipated to be low. A Log Kow higher close to 4 suggests that the rate of penetration of the substance may be limited by the rate of transfer between the stratum corneum and the epidermis. However, a molecular mass smaller than 500 g/mol are favourable to a dermal absorption.

According to the IH skin perm (QSAR), the dermal absorption of DPTH is 0%.

No mortality or clinical signs were observed in the acute study by dermal route in rats, and DPTH showed no allergic reaction in the LLNA.

10% of absorption is taken into account for the risk assessment.

Based on the low vapour pressure, DPTH is considered to be not a volatile substance. Indeed, the absorption by inhalation is expected to be low for DPTH based on the values of low water solubility and high log kow.

No mortality or clinical signs were observed in the acute study by inhalation inrats treated with 2.83 mg/L (the maximum attainable concentration).

100% of absorption is taken into account for the risk assessment (worst case).

 

DISTRIBUTION

No specific data is available on the distribution of DPTH.

No specific organ toxicity was observed in the 28 and 90 -day repeated toxicity studies at the maximal dose of 1000 mg/kg/day.

According to the QSAR pkCSM, the substance is well distributed into the body.

METABOLISM

No specific data is available on the metabolism of DPTH.

EXCRETION

Due to the low water solubility, the excretion of DPTH in the urines is expected to be low. According to the QSAR pkCSM, a high total clearance (hepatic & renal) is not expected. So, an excretion in the faeces is expected.