3-[(phenylcarbamoyl)amino]phenyl 4-methylbenzenesulfonate

Endpoint summary

Description of key information

INTRODUCTION

In accordance with the Section 8.8.1 of Annex VIII in Regulation (EC) No 1272/2008, the toxicokinetic profile of the substance was derived from all available substance-specific information as collated in the registration dossier. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017).

 

PHYSICOCHEMICAL PROPERTIES

The substance is a mono-constituent substance with a molecular weight of 382.43 g/mol.It is hydrolytically stable under the physiological condition.It is an off-white powder with no boiling point (test item changes at about 265°C), a melting point of 173.4 °C to 175.6 °C, and a vapour pressure of < 1.68 x 10^-5Pa (25°C). The registered substance has a low water solubility of 0.0269 mg/L at 20°C and a log Pow of 2.7 (25°C).Due to its low water solubility, the oral and dermal absorptions of the registered substance is expected to be limited. The particle size results of the registered substance are: D10 = 7.12 µm, D50 = 21.8 µm, and D90 = 81.5 µm, which suggests its dust contents of respirable particles are considered to be limited .Its low vapour pressure value suggests that the substance is poorly available as a vapour. 

ABSORPTION

No signs of oral absorption were seen in the results from the acute oral toxicity study in rats (Appl, 2017) and the combined repeated dose oral toxicity with reproduction/ developmental toxicity in rats (Fujii, 2021).

There are no signs of absorption via the dermal route in the acute dermal toxicity study in rats (Tsubokura, 2018) or the Local Lymph Node Assay in mice for skin sensitisation (Oroszlany, 2017).The registered substance is not a skin or eye irritantin vitro. Therefore, there is no indication to suggest that the dermal absorption may be enhanced by a repeated dosing regimen.

There were no signs of absorption following inhalation of the test item in rats (Nagy, 2021).

The available information suggests no signs of absorption via the oral, dermal and inhalation routes. However, in the absence of route-specific toxicokinetic information, and the relevant physico-chem data are within the range, a default value of 100% absorption rate is assumed for the oral, dermal and inhalation routes for risk assessment.

DISTRIBUTION

The moderate molecular weight and low water solubility of the registered substance are considered unlikely to allow it to disperse into the water compartment of blood for systemic distribution.There is no evidence to suggest the registered substance is distributed systemically or accumulated in the body in the available mammalian studies.

METABOLISM

The results of the OECD 422 study in rats did not show any evidence of enhanced liver metabolism up to the highest dose level of 1000 mg/kg bw/day. The substance was positive in the presence of metabolic activation in the chromosome aberration test using Chinese hamster lung fibroblasts, whereas it was negative without metabolic activation (Ogura, 2020). However, genotoxicity potential of TG_MD was not supported in other studies. It was negative in the Ames test both in the presence and absence of metabolic activation (Sarada, 2018) and in thein vivo micronucleus test in mice (Sakakibara, 2021). Overall conclusion was that metabolism did not influence genotoxicity. 

EXCERETION

There is no evidence to indicate the route of excretion. Given its moderate molecular weight and log Pow value, the registered substance may preferentially go through biliary excretion. Any test material that is not absorbed will be excreted in the faeces.

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100