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Toxicological information

Health surveillance data

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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

Reference
Name:
Unnamed
Type:
Constituent
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).