Di(morpholin-4-yl) disulphide

Endpoint summary

Description of key information

No experimental toxicokinetic study is available on DTDM. However, as per REACH guidance document R7.C (2014), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties. Based on the toxicological data and the physicochemical properties, absorption of the substance is expected by oral route, by dermal route and by inhalation. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The following remarks on the toxicokinetics of DTDM are based on the available studies. Experimental toxicokinetic studies were not available. However, as per REACH guidance document R7.C (2014), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties, including:

-Molecular weight: 236 g/mol

-Water solubility: 215 mg/L (20°C)

-Partition coefficient Log Kow: 2.67 (22°C)

-Vapour pressure: 0.004 Pa (25°C)

 

ABSORPTION

The physico-chemical properties of DTDM are favourable to the oral and dermal absorption: a value of log Kow between 1 and 4 (e.g. 2.67), a moderate water solubility (215 mg/l), a molecular weight below than 500 (236 g/mol).

Based on the experimental data, DTDM is well absorbed orally by rats after a single administration at a high dose (oral LD50 = 5600 mg/kg) or after repeated administration at the dose of 500 mg/kg (in a developmental toxicity study).

By dermal route, DTDM is sensitizer (in cobayes): the dermal absorption is confirmed.

Based on the low value of the vapour pressure, DTDM is considered to be not volatile. However, DTDM is a powder with a low particle size and a moderate water solubility, the absorption after inhalation is favourable.

The mean particle size, number in volume, of DTDM (4,4'-dithiodimorpholine) test item, is determined to be 42µm, with 10% of particles presenting a diameter less than 13µm, and 10% of particles presenting a diameter larger than 77µm.

A repeated toxicity study by inhalation is available, and no adverse systemic toxicity were showed in rats treated at 8.38 mg/l for 3 months. But local effects were observed and DTDM is considered to be irritating for the respiratory tract.

 

DISTRIBUTION

The physico-chemical properties of DTDM are favourable to the distribution of the substance in the body after absorption (log Kow, moderate water solubility, low molecular weight). A value of log Kow higher than 0 (e.g. 2.67) suggests a distribution into cells and the intracellular concentration may be higher than extracellular concentration.

However no accumulation is expected in the lung, adipose tissue, bone or stratum corneum based on the physico-chemical properties of DTDM.

METABOLISM

There is no data on metabolism on DTDM.

It is very difficult to predict the metabolic changes of a substance on the basis of physico-chemical information alone.

EXCRETION

The major route of excretion expected for DTDM is urine because the substances that are excreted in the urine tend to be water-soluble and of low molecular weight (below 300).