2-propylheptyl methacrylate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail.

Data source

Reference

Reference Type:

other: thesis

Title:

Unnamed

Year:

2002

Materials and methods

Objective of study:

metabolism

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl methacrylate

EC Number:

202-615-1

EC Name:

Butyl methacrylate

Cas Number:

97-88-1

IUPAC Name:

butyl methacrylate

Constituent 2

Reference substance name:

2-ethylhexyl methacrylate

EC Number:

211-708-6

EC Name:

2-ethylhexyl methacrylate

Cas Number:

688-84-6

IUPAC Name:

2-ethylhexyl methacrylate

Details on test material:

Methacrylic acid from Ineos Acrylics (Lot 98/42; purity > 99%), methyl methacrylate from Ineos Acrylics (Lot 98/15; purity > 99%), ethyl methacrylat from Atofina (Lot 011666; purity: > 99%), i-butyl methacrylate from Ineos Acrylics (Lot 98/15; purity 99%), n-butyl methacrylate from Ineos Acrylics (Lot 98/15; purity 99%), hexyl methacrylate from Röhm GmbH (Lot 78070243; purity > 98%), 2-ethylhexyl methacrylate from Röhm GmbH (Lot 78080370; purity > 98%), octyl methacrylate from Röhm GmbH (Lot 22-902-13914-28; purity > 98%)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

other: in vitro and intravenous in vivo

Applicant's summary and conclusion

Conclusions:

Using a reliable experimental method, the in vivo and in vitro investigations as well as the PBPK models developed from the data showed that alkyl-methacrylate esters are rapidly absorbed and are hydrolyzed at exceptionally high rates to methacrylic acid by high capacity, ubiquitous carboxylesterases. Further, the removal of the hydrolysis product, methacrylic acid, also is very rapid (minutes). For 2-EHMA the half-life was 23.8 minutes and 99.9 % was removed by first-pass metabolism in the liver.

Executive summary:

Using a reliable experimental method, the in vivo and in vitro investigations as well as the PBPK models developed from the data showed that alkyl-methacrylate esters are rapidly absorbed and are hydrolyzed at exceptionally high rates to methacrylic acid by high capacity, ubiquitous carboxylesterases. Further, the removal of the hydrolysis product, methacrylic acid, also is very rapid (minutes). For 2-EHMA the half-life was 23.8 minutes and 99.9 % was removed by first-pass metabolism in the liver.

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