2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

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

Adequacy of study:

key study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well-documented and acceptable for assessment

Reason / purpose for cross-reference:

reference to other study

Objective of study:

other: HYDROLYSIS OF PHOSPHOETHYL METHACRYLATE DIESTER AND PHOSPHOETHYL METHACRYLATE MONOESTER

Qualifier:

no guideline followed

GLP compliance:

no

Radiolabelling:

no

Species:

other: not applicable

Details on test animals or test system and environmental conditions:

not applicable

Route of administration:

other: not applicable

Vehicle:

unchanged (no vehicle)

Details on exposure:

Phosphoethyl methacrylate monoester or Phosphoethyl methacrylate diester at two concentrations (0.1 mM and 1 mM) ) was individually incubated
for 45 minutes with rat liver microsomes, or human liver S9, or rat liver S9 (1 mg/mL protein) in the presence or absence of cofactor NADPH (1 mM) under the physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37°C).

Duration and frequency of treatment / exposure:

45 minutes

Remarks:

Doses / Concentrations:
0.1 mM and 1 mM

No. of animals per sex per dose / concentration:

not applicable

Control animals:

other: not applicable

Positive control reference chemical:

no

Details on study design:

Phosphoethyl methacrylate monoester or Phosphoethyl methacrylate diester at two concentrations (0.1 mM and 1 mM) ) was individually incubated for 45 minutes with rat liver microsomes, or human liver S9, or rat liver S9 (1 mg/mL protein) in the presence or absence of cofactor NADPH (1 mM) under the physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37C). After incubation, the sample were taken out from the incubator and put in ice-bath and 200 uL of Acetonitrile containing 2% formic acid was added to each incubation vial. After a vortex, the whole solution was transferred to a microcentriguge tube and centrifuged for 5 min at 15000 rpm. The supernatant was transferred to a clean glass vial for Q-TOF LC/MS analysis of substrate loss or the hydrolysis metabolite formation.

Statistics:

Phosphoethyl methacrylate monoester or Phosphoethyl methacrylate diester at two concentrations (0.1 mM and 1 mM) ) was individually incubated for 45 minutes with rat liver microsomes, or human liver S9, or rat liver S9 (1 mg/mL protein) in the presence or absence of cofactor NADPH (1 mM) under the physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37C). After incubation, the sample were taken out from the incubator and put in ice-bath and 200 uL of Acetonitrile containing 2% formic acid was added to each incubation vial.

Preliminary studies:

not applicable

Details on absorption:

not applicable

Details on distribution in tissues:

not applicable

Details on excretion:

not applicable

Details on metabolites:

not applicable

Bioaccessibility (or Bioavailability) testing results:

not applicable

Conclusions:

Interpretation of results (migrated information): other: phosphoethyl methacrylate diester (diester) and phosphoethyl methacrylate monoester (monoester) are stable in the presence of rat or human liver tissue enzymes
The current study showed that both phosphoethyl methacrylate diester (diester) and phosphoethyl methacrylate monoester (monoester) are stable in the presence of rat or human liver tissue enzymes.

Executive summary:

To explore the enzymatic hydrolysis rates of both phosphoethyl methacrylate diester (diester) and phosphoethyl methacrylate monoester (monoester), two concentrations of diester and monoester(0.1 mM, 1mM) were incubated for 45 minutes with commercial rat liver microsomes, mouse liver S9, and human liver S9 (1 mg /mL) in the presence or absence of the cofactor NADPH (1 mM) under physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37°C). Following by enzyme deactivation and, centrifugation, levels of the parent esters were determined by high resolution Q-TOF/LC/MS analysis. Analysis results showed that both diester and monoester were poorly hydrolyzed in the current incubation condition, indicating that both diester and monoester are stable in current in vitro enzymatic hydrolysis condition.  

Description of key information

Basic TK in vitro/ex vivo

Phosphoethyl methacrylate monoester or Phosphoethyl methacrylate diester at two concentrations (0.1 mM and 1 mM) ) was individually incubated for 45 minutes with rat liver microsomes, or human liver S9, or rat liver S9 (1 mg/mL protein) in the presence or absence of cofactor NADPH (1 mM) under the physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37C).  After incubation, the sample were taken out from the incubator and put in ice-bath and 200 uL of Acetonitrile containing 2% formic acid was added to each incubation vial.  After a vortex, the whole solution was transferred to a microcentriguge tube and centrifuged for 5 min at 15000 rpm.  The supernatant was transferred to a clean glass vial for Q-TOF LC/MS analysis of substrate loss or the hydrolysis metabolite formation.

To explore the enzymatic hydrolysis rates of both phosphoethyl methacrylate diester (diester) and phosphoethyl methacrylate monoester(monoester), two concentrations ofdiester and monoester(0.1 mM, 1mM) were incubated for 45 minutes with commercial rat liver microsomes, mouse liver S9, and human liver S9 (1 mg /mL) in the presence or absence of the cofactor NADPH (1 mM) under physiological condition (pH 7.4 with 0.1 M phosphate buffer and 37°C). Following by enzyme deactivation and, centrifugation, levels of the parent esters were determined by high resolution Q-TOF/LC/MS analysis. Analysis results showed that bothdiester and monoester were poorly hydrolyzed in the current incubation condition, indicating thatbothdiester and monoester are stable in currentin vitroenzymatic hydrolysis condition.