Trimethylamine

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented publication, which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Toxicity of aliphatic amines in Uremia

Author:

Simenhoff, M.L., Ginn, H. E., and Teschan, P.E.

Year:

1977

Bibliographic source:

Trans.Am.Soc.Artif.INtern.Organs, 1988 Vol. XXIII p. 560 - 64

Materials and methods

Study type:

biological effect monitoring

Endpoint addressed:

other: Crossing of the Brain-Bloow-Barrier

Principles of method if other than guideline:

Some years ago it was found that amines, especially dimethylamine (DMA) and ethanolamine were raised in the blood, CSF and brain of uremic patients. We have always believed that since many of the major uremic symptoms reflecting toxicity are neurologic, these toxic substances must cross the blood brain barrier. Thus, we were concerned with the findings of Wootten and Hicks some years ago when they reported the large variety of phenolic and other organic acids isolated from dialysate, because they did not cross the B-B-B in significant quantity.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethylamine

EC Number:

200-875-0

EC Name:

Trimethylamine

Cas Number:

75-50-3

Molecular formula:

C3H9N

IUPAC Name:

N,N-dimethylmethanamine

Details on test material:

no data

Method

Ethical approval:

not specified

Details on study design:

Twenty-six patients with end-stage kidney disease (most of them on dialysis) had predialysis choice reaction time (CRT) and electroencephalograms (EEG) performed at the Vanderbilt Medical Center. At the same time a serum sample was obtained, and a total of 53 samples were subsequently measured for DMA and TMA. The results of the neurophysiological tests were not known at the time of blood amine determinations. The methods used for serum amine determinations have been previously described. Neurophysiological tests were done according to the method of Ginn and Teschan.

Results and discussion

Results:

There is an excellent correlation between the predialysis creatinine and CRT with a p value < 0.001 (Figure 1), whereas there is a poor correlation with the EEG as shown in Figure 2 (p < 0. 50). Serum DMA also correlates better with CRT with a p value < 0. 01 (Figure 3). The relationship of TMA to CRT and EEG gave p value of < 0. 001 and < 0. 003, respectively. The DMA and TMA levels show a statistically significant correlation with both CRT and EEG suggesting that these compounds produce more diffuse and toxic neurologic consequences.

Any other information on results incl. tables

Amine levels above 200 µg % are usually associated with symptoms. Should these toxic effects be confirmed, the metabolic sources of amines would become important. We have previously reported that an abnormal bacterial flora exists high up in the small intestine in advanced renal failure and that alteration of this flora, by nonabsorbable antibiotic administration, reduces blood amine levels with concomitant improvement in symptomatology.

Applicant's summary and conclusion

Executive summary:

In 1977 Simenhoff et al. investigated the prevalence of DMA and TMA in patients suffering under chronic renal failure. Fifty-three samples in 26 patients were analyzed for aliphatic amines (DMA and TMA), and the levels correlated with 2 neurophysiological tests, choice reaction time (CRT), and electroencephalogram (EEG). A significant correlation was found between TMA and CRT and EEG (p < 0.001 and 0. 003, respectively) and between DMA and CRT (p < 0.01).

These amines reflect part of the spectrum of toxic compounds which accumulate in uremia. Dissociation of neurophysiological functions may be helpful in evaluating various classes of potentially toxic compounds found in renal failure, as exemplified by short-chain aliphatic amines.