Registration Dossier

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Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

TOXICOKINETIC ASSESSMENT: Condensation products of phenol and salicylaldehyde

 

INTRODUCTION

 

In accordance with the section 8.8.1 of Annex VIII in Regulation (EC) No 1272/2008, the toxicokinetic profile of the registered substance, “condensation products of phenol and salicylaldehyde (MEH-7500)" has been derived from all available information collated in the dossier. The assessment is based on the “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance” (ECHA, June 2017).

 

PHYSICOCHEMICAL PROPERTIES

 

MEH-7500is a UVCB substance, composed of the dehydration-condensation reaction products of 2-hydroxy benzaldehyde and phenol, with its moderate molecular weight ranging from 292 to 690 g/mol (292 g/mol with 64%, 491 g/mol with 22% and 690 g/mol with 8%). It is a red to reddish brown solid with a boiling range of 242.18°C – 320.69°C accompanied by decomposition and a vapour pressure of 17 hPa at 75°C. The substance has a relatively high water solubility of 2507 mg/L at 20 °C with the main constituent having a moderate log Pow value of 3.93 (estimated value using KOWWIN v1.68, EPI SUITE v4.11). Due to its relatively moderate molecular weight range, relatively high water solubility and the moderate log Pow value of the main constituent, the substance is expected to be absorbed via the oral and dermal routes; although the absorption of the constituent with the higher end of molecular weight range may occur at a lesser extent. The particle size results of the registered substance are: D10 = 26.22 µm, D50 = 197.131 and D90 = 534.74 µm, which suggest its dust contents of respirable particles are not significant for inhalation exposure. Its low vapour pressure value suggest that the substance is poorly available as a vapour. 

 

ABSORPTION:

The results of available combined repeated dose toxicity study with the reproduction/developmental toxicity screening test and its preliminary range-finding study in rat show signs of absorption. This is supported by the above-mentioned physico-chemical properties.

 

There are no signs of absorption via the dermal route in the acute dermal toxicity study in rats. However, a sign of dermal absorption of the registered substance is evidenced by the positive skin sensitisation response in the local lymph node assay (LLNA) in mice. The registered substance is a skin irritant based on thein vitroassay and therefore the irritant property of the registered substance may have damaged to the skin surface and subsequently enhanced a penetration of substance in the skin.

 

There are no inhalation studies available for the registered substance. However, due to its physico-chemical properties, inhalation is not considered to be the most significant route of exposure.

 

Distribution

The high water solubility and relatively small molecular weight of the major constituent of the test material will allow it to disperse into the water compartment of blood for distribution. The positive result of the LLNA suggests that the registered substance binds to carrier proteins in the blood once in enters the circulatory system. The estimated log Pow value of the main constituent indicates the registered substance may be accumulated in body fat.

 

Metabolism

The results of the OECD 422 and its range-finding study in rats did not show any strong evidence of enhanced liver metabolism. Although a non-adverse increase in the liver weights was observed, there are no corroborative changes in clinical chemistry parameters or histopathological findings.

 

Excretion

There is no evidence to indicate the route of excretion. However, given its moderate molecular weight range and high water solubility, the kidney is expected to be a significant route of excretion for the registered substance. Any test material that is not absorbed will be excreted in the faeces.

 

References

ECHA (2017) Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7c: Endpoint specific guidance, Version 3.0, June 2017

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