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Description of key information

Based on the physical and chemical properties and the toxicological data available, DPTU is absorbed by oral and dermal route. DPTU is well distributed in the body and induded a thyroid toxicity.
A specific in vitro study on metabolism was found on DPTU. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU.

Key value for chemical safety assessment

Additional information

The following remarks on the toxicokinetics of DPTU are based on the available studies. Only one experimental toxicokinetic study is available. However, as per REACH guidance document R7.C (May 2008), information on absorption, distribution, metabolisation and excretion may be deduced from the physicochemical properties, including:

-Molecular weight: 228.3 g/mol

-Water solubility: 24.37 mg/L (20°C)

-Partition coefficient Log Kow: 2.0

-Vapour pressure: 0.001 Pa (25°C)

 

ABSORPTION

The physicochemical characteristics of DPTU (log Kow = 2) and the molecular mass (223.3 g/mol) are in the range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion (with a molecular weight below 500, and a log Kow between -1 and 4). This assumption of an oral absorption is confirmed in the repeated toxicity study (thyroid toxicity at 250 mg/kg) in rats.

With a water solubility between 1 and 100 mg/L, dermal absorption is anticipated to be low to moderate. This assumption of a dermal absorption is confirmed by the skin sensitisation data as DPTU is a strong skin sensitizer.

However, DPTU is a solid with a low vapour pressure (< 1 Pa) : DPTU is not a volatile substance.

 

DISTRIBUTION and METABOLISM

As a small molecule a wide distribution of DETU is expected.

Moreover, the molecule is lipophilic (log Kow > 0), it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.

This assumption is confirmed by the changes shown in the repeated dose toxicity studies following oral application: effects on thyroid were specific to the oral administration of DETU in rats.

 

Only one study on metabolism is available on DPTU (Samuelsson 2011) :

Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical- and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU works as a contact allergen has not been described; thus, the aim of the present study was to investigate if DPTU is a prohapten that can be activated by skin metabolism. The metabolic activation and covalent binding of 14C-labeled DPTU to proteins were tested using a skinlike cytochrome P450 (P450) cocktail containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6, 2E1, and 3A5) and human liver microsomes. The incubations were carried out in the presence or absence of the metabolite trapping agents glutathione, methoxylamine, and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography, LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU.

ELIMINATION

Due to the small weight molecular, DPTU is probably excreted in the urines.