p-toluenesulphonyl isocyanate

Endpoint summary

Description of key information

No studies available, toxicokinetic assessment based on physical/chemical parameters

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Background

PTSI is extremely reactive with water/moisture, the molecule reacts instantaneously and exothermic to create p-toluenesulfonyl amide (PTSA) under production of carbon dioxide (CO2). The reaction is not pH specific and will take place in any aqueous medium. Due to this extreme reactivity, the toxicokinetic assessment is performed on PTSA instead of PTSI.

No study is available addressing the toxicokinetics of PTSA. Therefore, the toxicokinetic assessment is based on the physical/chemical properties of PTSA.

 

Physical/chemical properties

PTSA is a strong organic acid (solid) that is soluble in water, alcohols, and other polar organic solvents. The following physical/chemical properties are of interest for assessing the toxicokinetics:

·        Water solubility 3.1 g/L

·        Molecular weight: 171.23

·        Log Kow: 0.6

·        Vapour pressure:<2.86.10^-7kPa

Absorption

PTSA is hydrophilic (based on the high water solubility) and relatively small (low molecular weight; Mw <500). Therefore oral/GI-absorption by passive diffusion is expected to be high. In a 90-day repeated dose oral toxicity, PTSA was found to cause a treatment-related reduction in body weight gain and minimal urethelial hyperplasia at the highest dose level of 767 mg/kg bwt/day. This finding indicates that oral absorption had occurred.

Respiratory exposure to PTSA is unlikely to occur on a large scale, due to the very low vapour pressure of the substance (<2.86.10^-7kPa). However, some respiratory exposure may occur. Any inhaled PTSA may be absorbed through the inhalation tract to the same extent and for the same reasons as for oral absorption.

After dermal exposure, dermal absorption is indicated due to the liquid state of the reaction product of PTSI and the low vapour pressure. Although the molecular weight is >100, which is less favourable for dermal uptake, the molecule is not too large as it is <500. Based on the high water solubility of PTSA acid, dermal uptake is expected to be moderate to high. Furthermore, the high water solubility indicates that the substance may readily partition from the stratum corneum into the epidermis. Moreover, the reactivity of PTSI when coming in contact with water may trigger skin irritation, which may favour dermal absorption.

 

Distribution

The relatively low molecular weight and high water solubility of PTSA favour its distribution throughout the body, especially into the extracellular spaces. Due to its highly hydrophilic character it is anticipated that it will tend to partition readily to aqueous compartments/tissues. It is less likely that it will partition to the adipose tissues and lipophilic layers like the stratum corneum.

 

Metabolism and excretion

No studies on metabolism and excretion are available. The low molecular weight (Mw<300) and high water solubility of PTSA will favour rapid excretion via the urine.

 

Conclusions

Although no study addressing the toxicokinetic properties of PTSA is available, it is assumed that it can readily be absorbed via the oral, dermal and inhalation route and will readily distribute throughout the aqueous compartments of the body, based on its physicochemical properties.

For risk assessment, oral and dermal absorption are assumed to be similar (100%). In absence of information on the inhalation route, a default absorption of twice the oral absorption is assumed for inhalation absorption.

It is also assumed that PTSA will be rapidly excreted via the urine.