Dimethylamine

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Increase in Human Exposure to Methylamine Precursors of N-Nitrosamines after Eating Fish

Author:

Zeisel, S.H. and DaCosta, K.-A.

Year:

1986

Bibliographic source:

CANCER RESEARCH 46, 6136-6138, December 1986

Materials and methods

Study type:

human medical data

Endpoint addressed:

not applicable

Principles of method if other than guideline:

For 2 days volunteers ingested a control diet of known methylamines content. On Day 3 of the study, fish was substituted as the chief constituent of the luncheon and dinner meals. On Day 4, the subjects returned to the control diet.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dimethylamine

EC Number:

204-697-4

EC Name:

Dimethylamine

Cas Number:

124-40-3

Molecular formula:

C2H7N

IUPAC Name:

N-methylmethanamine

Details on test material:

diet of known methylamine content (fish)

Method

Type of population:

general

Ethical approval:

not specified

Details on study design:

For 2 days volunteers ingested a control diet of known methylamines content. On Day 3 of the study, fish was substituted as the chief constituent of the luncheon and dinner meals. On Day 4, the subjects returned to the control diet.

Results and discussion

Results:

Urinary excretion of dimethylamine excretion increased more than 4- fold after fish was eaten (from 5.6 to 24.1 µmol/24h/kg of body weight)

Any other information on results incl. tables

Fish and ham were the only foods which contained DMA in the foods ingested as part of the experimental diets. On control days, subjects ingested 6.7 µmol of DMA per day. On the day fish was eaten, subjects consumed 754 µmol DMA per day. DMA excretion was more than 4 times greater on the day that fish was eaten than on the control days (24.1 ± 3.5 versus 5.6 ± 0.2 µmol/24 h/kg of body weight; mean ± SE; P < 0.01). On the day after fish was eaten, DMA excretion remained elevated, being 2.8 times greater than on the control days (15.9 ± 2.8 /µmol/24 h/kg of body weight; mean ±SE; P < 0.05).

Applicant's summary and conclusion

Conclusions:

Fish and ham were the only foods which contained DMA in the foods ingested as part of the experimental diets. On control days, subjects ingested 6.7 µmol of DMA per day. On the day fish was eaten, subjects consumed 754 µmol DMA per day. DMA excretion was more than 4 times greater on the day that fish was eaten than on the control days (24.1 ± 3.5 versus 5.6 ± 0.2 µmol/24 h/kg of body weight; mean ± SE; P < 0.01). On the day after fish was eaten, DMA excretion remained elevated, being 2.8 times greater than on the control days (15.9 ± 2.8 /µmol/24 h/kg of body weight; mean ±SE; P < 0.05).

Executive summary:

DMA is readily transported from blood to gastric fluid. The other precursor needed for the formation of nitrosamine is nitrite, which is formed from dietary nitrate in the oral cavity and stomach by reactions mediated by bacterial enzymes. People ingest from 10 to several hundred, mg of sodium nitrate per day in food and water. The acidic conditions of the stomach favor the formation of nitrous anhydride and nitrosyl compounds which nitrosate amines to form nitrosamines. NDMA is rapidly formed when DMA and nitrite are mixed with gastric juice in a test tube or in the stomach of the dog. The in vivo formation of nitrosamines has clinical significance, as the same tumors are produced in experimental animals that are fed amine plus nitrite, as are formed in those fed the corresponding nitrosamine. The formation of NDMA in vivo in humans has not been well documented because this nitrosamine is rapidly metabolized. However, there is direct evidence that the nonmetabolizable nitrosamine, nitrosoproline, is synthesized in humans following the ingestion of an amine (proline) and nitrate. Although it appears that most of the ingested methylamine was rapidly excreted by humans, it is possible that significant amounts of NDMA could have been formed in vivo, as nitrosamines are of concern at very low concentrations (ppm).