Acrylic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

Metabolic in-vitro studies on tissue slices and homogenates from rats (F344 and Sprague Dawley), using 1-14C-labelled AA. The rate of oxidation [expressed as nmol CO2/h per g tissue or mg protein and kinetic parameters (pseudo-Km and Vmax) were determined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Acrylic acid

EC Number:

201-177-9

EC Name:

Acrylic acid

Cas Number:

79-10-7

Molecular formula:

C3H4O2

IUPAC Name:

prop-2-enoic acid

Details on test material:

- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: 98 %
- Supplier: Rohm and Haas Company

- Radiochemical purity (if radiolabelling): > 98 % and 95 %, respectively
- Specific activity (if radiolabelling): 0.1-0.5 mCi/mmol and 1.44 mCi/mmol, respectively
- Locations of the label (if radiolabelling): [1-14C]Acrylic acid
- Supplier: Sigma Chemical Co. (St. Louis, MO) and Chemsyn Science Laboratories (Lenexa, KS), respectively

Specific details on test material used for the study:

- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: 98 %
- Supplier: Rohm and Haas Company

- Radiochemical purity (if radiolabelling): > 98 % and 95 %, respectively
- Specific activity (if radiolabelling): 0.1-0.5 mCi/mmol and 1.44 mCi/mmol, respectively
- Locations of the label (if radiolabelling): [1-14C]Acrylic acid
- Supplier: Sigma Chemical Co. (St. Louis, MO) and Chemsyn Science Laboratories (Lenexa, KS), respectively

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

other: Fischer 344 and Sprague Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Wilmington, MA)
- Weight at study initiation: 249 ± 50 g (Fischer 344); 386 ± 120 g (Sprague-Dawley)
- Housing: 1-2 per cage
- Diet (ad libitum): Purina Certified Lab Chow Checkers (Purina, St. Louis, MO)
- Water: ad libitum

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

other: The kidney and liver were the organs showing the highest oxidation rates. All tissues were able to oxidize AA to a certain extent. Lung, glandular stomach, heart, spleen, small and large intestine oxidized AA at rates that were between 10 and 40 %.

Toxicokinetic parameters 2

Toxicokinetic parameters:

other: Oxidation of AA in Fischer 344 rat kidney and liver slices were described by pseudo MIchaelis-Menten kinetics. The pseudo Km value did not vary between kidney and liver: ca. 0.5 mM. However, the pseudo Vmax in kidney was approx. twice the value in liver.

Any other information on results incl. tables

The kidney and liver were the organs showing the highest oxidation rates, with maximal velocities of 4 and 2 µmol/h/g, respectively. The metabolic conversion rate was similar in both strains with no difference between slice model and homogenate. All tissues were able to oxidize AA to a certain extent, but with considerable variation. Lung, glandular stomach, heart, spleen, small intestine and large intestine oxidized AA at rates that were between 10 and 40 % of the rate measured in liver. The remaining tissues (forestomach, brain, skin, fat, and muscle) oxidized AA at less than 10 % of the rate observed in the liver.

Compared to the mouse (see Black et al., 1993), the absolute rates per g tissue in the rat are 2 - 3 x higher than in the mouse.

Oxidation of AA in Fischer 344 rat kidney and liver slices were described by pseudo MIchaelis-Menten kinetics. The pseudo Km value did not vary between kidney and liver: approx. 0.5 mM. However, the pseudo Vmax in kidney was approx. twice the value in liver. At relatively low concentrations, i.e. well below km, AA oxidation would follow apparent first-order kinetics, and the half-life of AA in liver and kidney would be approx. 10 min or less.

AA tissue-to-blood partition coefficients were measured in homogenates by micropartitioning. Relatively little variation between tissues in the partition coefficient was observed, with values ranging between 0.9 (fat) and 2.1 (brain).