Phenyl methacrylate

Endpoint summary

Description of key information

PHMA is likely to be readily absorbed by all routes. Due to the low vapour pressure, the dermal route is the primary route of exposure, since inhalation is unlikely. The ester is rapidly hydrolysed by carboxylesterases to methacrylic acid (MAA) and Phenol. The primary metabolite, MAA, is subsequently cleared rapidly from blood by standard physiological pathways, with the majority of the administered dose being exhaled as CO2. Phenol is conjugated with with Glucuronic acid or Sulphate and renally excreted. Based on physicochemical properties, no potential for bioaccumulation is to be expected.

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

Absorption

Oral absorption

The physicochemical properties of PHMA (log P = 2.7) and the molecular weight of162.19g/mol are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion.

For chemical safety assessment an oral absorption rate of 100% is assumed as a worst case default value in the absence of other data.

 

Dermal absorption

Based on a QSAR Prediction of Dermal Absorption (extract from Heylings JR, 2013) PHMA is predicted on the basis of their molecular weight and lipophilicity to have a relatively low ability to be absorbed through the skin. The predicted flux was 4.843 µg/cm²/h..

However, for chemical safety assessment, a dermal absorption rate of 100% was assumed as worst case default value.

 

Inhalative absorption

Due to the low vapour pressure of PHMA (0.5 hPa at 20°C), exposure via inhalation is unlikely. For chemical safety assessment an inhalative absorption rate of 100% is assumed as a worst case default value in the absence of other data.

 

Distribution

As a small molecule a wide distribution can be expected. No information on potential target organs is available.

 

Metabolism and excretion

Ester hydrolysis has been established as the primary step in the metabolism of methacrylate esters. Carboxylesterases are a group of non-specific enzymes that are widely distributed throughout the body and are known to show high activity within many tissues and organs, including the liver, blood, GI tract, nasal epithelium and skin (Satoh & Hosokawa, 1998; Junge & Krish, 1975; Bogdanffy et al., 1987; Frederick et al., 1994). Those organs and tissues that play an important role and/or contribute substantially to the primary metabolism of the short-chain, volatile, methacrylate esters are the tissues at the primary point of exposure, namely the nasal epithelia and the skin, and systemically, the liver and blood. For PHMA mostly the same would be the case except that because of the lower vapour pressure and hence lower likelihood of inhalation exposure the involvement of the nasal epithelium is less likely.

Ester hydrolysis of PHMA would result in Methacrylic acid and Phenol. According to EFSA (2013)“Conjugation with glucuronic acid to phenyl glucuronide and sulphation to phenyl sulphate seem to be the major metabolic pathways in mammals. The fraction of phenol which is not directly conjugated can be the substrate of oxidative metabolism: 1,4-dihydroxybenzene (hydroquinone) and. to a much lower extent, 1,2- dihydroxybenzene (catechol) are also produced in the body as a result of phenol oxidation, principally catalysed by cytochrome P4502E1, with the intermediate formation of 1,4-benzoquinone and 1,2- benzoquinone. The quinone metabolites, while undergoing similar phase II metabolic reactions as phenol itself, i.e. glucuronidation and sulfation, are likely to play a role in the toxicity of phenol.

The metabolism of phenol is saturable. At lower oral doses of phenol, the sulfo-conjugation seems to be the predominant metabolic pathway in humans, rats and mice. As the phenol dose increases, glucuronidation as well as the formation of oxidative metabolites increase. Data in humans and laboratory animals support that phenol is rapidly excreted in urine (mostly as phenyl sulfate and phenyl glucuronide), and that it does not accumulate in the body.”

Methacrylic acid is cleared rapidly from blood by standard physiological pathways, with the majority of the administered dose being exhaled as CO2.

 

Reference

EFSA (European Food Safety Authority),Scientific Opinion on the toxicological evaluation of phenol,EFSA Journal 2013;11(4):3189, available online: http://www.efsa.europa.eu/de/efsajournal/pub/3189.htm