N,N-dimethylacrylamide

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Effect of acrylamide and related compounds on glycolytic enzymes in rat sciatic nerve in vivo

Author:

Sakamoto J, Hashimoto K

Year:

1985

Bibliographic source:

Arch Toxicol (1985) 57: 282-284

Materials and methods

Test guideline

Qualifier:

no guideline required

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylacrylamide

EC Number:

220-237-5

EC Name:

N,N-dimethylacrylamide

Cas Number:

2680-03-7

Molecular formula:

C5H9NO

IUPAC Name:

N,N-dimethylacrylamide

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 192±8 g
- Housing: three to four per plastic cage containing wooden flakes
- Diet (e.g. ad libitum): laboratory chow

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

15, 30 and 45 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
15 mM
Basis:
nominal in water

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Details on study design:

Preparation of sciatic nerve for enzyme assay. Rats were killed by decapitation after the three different dosing periods, and the sciatic nerves of both lower extremities were quickly removed from the sciatic notch to the ankle region of the tibial nerve with a part of the common peroneal nerve, weighed, frozen in liquid N2, and stored at -80ºC until use. The frozen nerves were crushed with a stainless steel tissue crusher pre-chilled in liquid N2, suspended in 10 vol ice-cold 0.05 M tris-phosphate buffer, pH 7.4, containing 1 mM EDTA and 1 mM dithiothreitol, and gently homogenized using a Potter-Elvehjem homogenizer with teflon pestle. The homogenates were centrifuged at 100,000 g for 60 min at 4ºC and the resultant supernatants were used for enzyme assays.

Enzyme assays. Activity of both GAPDH and total enolase in sciatic nerve samples was determined as described in the report by Sakamoto and Hashimoto (1985). The protein content of the assay samples was determined by the method Lowry et al. (1951).

Statistical method. Comparisons of mean values in the test groups versus the controls were performed using the Student's t-test.

Results and discussion

Details on results:

After 15 days of treatment, N,N-dimethylacrylamide, a non-neurotoxic analogue of acrylamide, produced moderate body weight loss without causing any change in the activity of either enzyme (GAPDH and enolase). After 30 days of treatment N,N-dimethylacrylamide produced body weight loss and reduction in GAPDH activity. After 45 days of treatment, N,N-dimethylacrylamide also produced body weight loss and inhibition of GAPDH.

N,N-dimethylacrylamide produced inhibition of GAPDH as well as body weight loss after 30 days without causing any signs of neuropathy. This compound did not inhibit enolase even after 45 days' treatment, although it has a strong inhibitory effect on mouse brain total enolase (Sakamoto and Hashimoto 1985). From the present observations, it might be suggested that even non-neurotoxic acrylamide analogues have an inhibitory effect on GAPDH in vivo.