Methyl benzoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

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

Data source

Reference

Reference Type:

publication

Title:

Studies on absorption and excretion of drugs. IX. Relation between chemical structure and absorption rate. (1). Effects of the number and the position of OH-groups on the intestinal absorption rate of benzoyl derivatives

Author:

Nogami H, Hanano M, Yamada H

Year:

1968

Bibliographic source:

Chemical and Pharmaceutical Bulletin 16(3), 389-395

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Elucidate by the kinetic method the relationship between chemical structure and intestinal absorption rates. The recirculation perfusion method based on that of Schanker LS et al (1958) was used with a suitable modification.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl benzoate

EC Number:

202-259-7

EC Name:

Methyl benzoate

Cas Number:

93-58-3

Molecular formula:

C8H8O2

IUPAC Name:

methyl benzoate

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 270±30g
- Fasting period before study: 24 h prior to the experiment
- Housing: no data
- Individual metabolism cages: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

other: perfusion

Vehicle:

other: 0.9 % NaCl solution in water adjusted to pH 6

Details on study design:

The small intestine was exposed by a midline abdominal incision and cannulated at the immediately distal part and at the 20 cm distal part to the entrance of the bile duct with glass cannulae having inside diameter of 2.5 mm and outside diameter of 3.5 mm. The intestine was replaced in the abdomen, the incision was closed and these cannulae were joined to a perfusion pump. The small intestine was first cleared of particulate matter by perfusion with 100 ml of 0.9% NaCl solution maintained at 37°C. Then the sample solution (50, 100 or 200 mL) maintained at 37°C was perfused by recirculation from the proximal to the distal at a rate of 20 mL per min. After recirculation for the time previously programmed, the sample solution was recovered and the intestinal lumen was thoroughly washed with 100 ml of 0.9% NaCl solution. The remaining drug was completely collected in a measuring flask and measured. The experiments for each sample solution were repeated three times or more with alteration in the perfusion period.
Two hundred milliliters of the sample solution and washings were transferred into a 1 liter-measuring flask and the volume was made up to 1 liter with distilled water. These recovered sample solutions were diluted with 0.1 N HCl and optical densities measured at 230 mµ for methyl benzoate.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption rates were compared by means of the first-order rate coefficients obtained using equation: log(D/D0) =-0.434kt/V=-k't (1). In equation, t is the perfusion time, D0 and D are the drug amounts in the solution at t=0 and at t=t, k and k' are constants and V is the volume of the perfusion solution. from the results of the preliminary test, it was found that the volume changes during the perfusion experiment were negligible (less than 5%) and that the logarithmic plots of the residual ratio vs. time gave straight lines, so that the mathematical relation shown in equation (1) could be applied. In equation (1), k' can be obtained as the slope of the straight line from the logarithmic plot of the residual ratio against time and k can be calculated by using equation (2): k=2.303xVxk'. Absorption rate coeficient k for Methyl benzoate was determined: 1.43.

Applicant's summary and conclusion

Conclusions:

Absorption rate coefficient for Methyl benzoate is 1.43.
The absorption rate coefficient of 2 mM Methyl benzoate in small intestine of rat is 1.43.

Executive summary:

Male rats, weighing 270 +/-30 g were used after a 24 hour fast. Water was allowed ad libitum. Vehicle was 0.9% saline adjusted to pH 6.0. The perfusion sample size was 50, 100 or 200 mL maintained at 37 °C and was perfused by recirculation at a rate of 20 mL per minute. After recirculation, the sample solution was recovered and the intestinal lumen was washed. The remaining drug was completely collected in a measuring flask and measured. The experiments for each sample solution were repeated three times or more with alteration in the perfusion period. The intestinal absorption rate of the test material was evaluated. The absorption rate coefficient of 2 mM Methyl benzoate was 1.43.