tert-butyl acrylate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

metabolism

Qualifier:

no guideline followed

Principles of method if other than guideline:

Tert-butyl acrylate was tested for relative rates of hydrolysis by mammalian esterase.

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): t-Butyl acrylate
- Physical state: liquid
- Analytical purity: 99.5% a.i.
- Lot/batch No.: 669-8784
- Stability under test conditions: considered as stable

Radiolabelling:

no

Details on test animals or test system and environmental conditions:

Porcine hepatic esterase as a suspension in 3.2 M ammonium sulfate solution was procured from Sigma, USA. According to the label information provided by the supplier, the concentration of the enzyme was 15 mg protein/mL (biuret) and the activity was 250 units/mg.

Route of administration:

other: in vitro application in liquid medium

Details on exposure:

- The assays were conducted in a total volume of 10 mL in capped vials in 0.1 M sodium phosphate buffer at pH 7.4 at 37°C, under conditions (0.15 units of enzyme/mL with aliquots removed for analysis at 2 and 5 min after the addition of enzyme to the substrate) that approximate the initial rate.
- The reaction conditions were determined based on pilot studies. Reactions were terminated by the addition of an equal volume 1.0 M phosphoric acid. A terminal hydrolysis sample was also taken at 3 hr following reaction initiation for analysis.
- A negative control reaction with buffer and each test compound but no enzyme was conducted at each concentration for the 2 and 5 min time points.
- The reaction rates are determined by comparing the peak area of the hydrolysis reaction product at 3 hours (terminal hydrolysis sample) to the peak area at 2 and 5 minutes following reaction initiation. The results reported are the average of three determinations for each test material.

Duration and frequency of treatment / exposure:

2 min/ 5 min/ 3 h

Dose / conc.:

0.2 other: mM

Dose / conc.:

0.5 other: mM

Dose / conc.:

2 other: mM

Control animals:

other: negative control without enzyme

Details on dosing and sampling:

Reaction rates were determined by loss of substrate and formation of the hydrolysis product. Product formation was monitored by analyzing aliquots of the quenched reaction by HPLC (Hewlett Packard Series 1100 HPLC system).

Metabolites identified:

no

Details on metabolites:

T-butyl acrylate did not appear to be substrate for this mammalian esterase, since little or no enzyme-catalyzed hydrolysis was detected under the reaction conditions.

Description of key information

Tert.-butyl acrylate, like other lower alkyl acrylates, is a reactive monomer. The principle detoxification routes of acrylate esters are the conjugation with glutathione followed by the excretion of the corresponding mercapturate and the hydrolysis by carboxyl esterases to acrylic acid and the alcohol (DeBethizy 1987)

Physicochemical and steric parameter may influence the rate of these metabolic degradation pathways. Overall the lower acrylates show a low toxicity profile (local effects on the port of entry and no to minor systemic effects) and are fast detoxified and excreted.

(see attached toxicokinetic statement for tert.-butyl acrylate)