Methylamine

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported, published 2001

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:

Methylamine in human urine

Author:

Mitchell, S.C and Zhang, A.Q

Year:

2001

Bibliographic source:

Clinica Chimica Acta 312 (2001) 107–114

Materials and methods

Study type:

biological effect monitoring

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Examination of urine samples after receiving oral doses (15 mmol) of known food components, betaine (1.76 g), carnitine (2.97 g), choline (2.10 g), creatinine (1.70 g) and lecithin (11.65 g, mol. wt. 776.7) on 5 different & separate occasions, at least 2 weeks apart.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylamine

EC Number:

200-820-0

EC Name:

Methylamine

Cas Number:

74-89-5

Molecular formula:

CH5N

IUPAC Name:

methanamine

Details on test material:

Anhydrous betaine ((carboxymethyl.trimethyl-ammonium hydroxide inner salt), DL-carnitine hydrochloride ((3-carboxy-2-hydroxypropyl)trimethyl- ammonium chloride., choline chloride ((2-hydroxy- ethyl)trimethylammonium chloride), isopropylamine (2-aminopropane) and methylamine hydrochloride were obtained from Sigma (Dorset, UK.) Anhydrous creatinine (2-amino-1-methyl-4-imidazolidinone) and lecithin (L-a-phosphatidyl choline, from soya beans) were obtained from British Drug House (Merck) (Dorset, UK). All other chemicals and reagents were of analytical grade and freely available within the laboratory

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

A total of 203 unrelated and randomly selected volunteers(102 male, age range 19–47 years, 22.2 ± 4.5, mean ± S.D.; 101 female, age range 19–48 years, 21.6 ± 5.0. were recruited from the staff and students of St. Mary’s Hospital Medical School, London. All subjects were in good health and none had been exposed to recent drug therapy or were taking medication at the time of the study. Nineteen subjects (9 male) smoked cigarettes (>20/day) and 175 (88 male) consumed alcohol, with 43 (30 male) being regular drinkers (20 + units/week). Volunteers maintained their normal diets while collecting complete 0–24 h urine samples.

Results and discussion

Results:

1. Males excreted more methylamines than females.
2. There were no significant differences between alcohol drinkers and abstainers, smokers and non-smokers.
3. There was a wide range (37-fold) within the daily methylamine output
4. see further in "Any other information"

Any other information on results incl. tables

Assay

Methylamine was clearly resolved from other volatile components within the head-space gas under the chromatographic condition employed. Instrument response was linear over the range of the calibration curves (r>0.99; P<0.01) and the recovery of added methylamine after sample processing was 99.3+7.5%.

Dietary sources of methylamine

None of the 41 different food products examined, containing representatives from the meat, fish and seafood, fruit and vegetable, dairy produce and cereal categories, produced any large increases in urinary methylamine output following ingestion. When compared to control values slight, but statistically significant (t-test), increases were observed following the consumption of several fish and seafoods including clam, crab, haddock, halibut, octopus and tuna as well as the fruit and vegetables, pear, peas and tomato. The values after plaice, banana and bread consumption were also raised and may have reached statistical significance if a greater number of subjects had been examined (Table 1). Similar results were obtained for the dietary chemicals. Although the numerical values rose, the wide variation observed between subjects meant that following ingestion of the five compounds investigated, only creatinine gave a statistically significant (t-test) rise in methylamine levels in subsequent urine samples. However, to place these urinary values into perspective, a total conversion of one of these dietary chemicals to produce 15 mmol of the amine is equivalent to 465 mg methylamine

Table 1. Urinary methylamine production from foods (227 g) following human ingestion
Foodstuff	Methylamine (mg/8h)	Foodstuff	Methylamine (mg/8h)
Meats		Fruit and vegetables
beef	2.00 ± 0.47	apple	3.63 ± 1.58
chicken	1.94 ± 0.73	banana	4.99 ± 0.99
duck	2.60 ± 0.29	carrot	3.55 ± 0.71
lamb	1.44 ± 0.38	cauliflower	4.66 ± 1.82
lamb's liver	3.75 ± 1.21	orange	3.53 ± 1.41
pork	2.30 ± 1.08	peanut	4.71 ± 2.02
		pear	5.11 ± 0.56^T
		peas	5.18 ± 1.07^T
		pineapple	3.26 ± 1.26
Fish		potato	3.31 ± 1.07
cod	4.37 ± 3.34	soyabean	2.66 ± 0.37
cod roe	4.18 ± 0.03	tomato	5.86 ± 1.21^T
coley	3.59 ± 1.06
haddock	5.85 ± 1.38^T
halibut	5.45 ± 0.11^T
lumpfish roe	2.94 ± 0.11	Dairy produce
plaice	6.98 ± 4.40	cheese	3.97 ± 1.81
skate	3.73 ± 1.03	eggs	2.93 ± 2.08
trout (rainbow)	3.24 ± 1.23	milk	4.46 ± 1.20
tuna	6.32 ± 0.12^T
whiting	2.64 ± 1.21
		Cereal products and miscellaneous
		biscuit	2.22 ± 0.07
Seafoods		bread	5.39 ± 1.89
clam	7.55 ± 3.11^T	mushroom	4.45 ± 3.15
cockles	3.93 ± 1.00	rice	4.90 ± 1.74
crab	7.07 ± 0.99^T
octopus	5.90 ± 1.70^T
prawn	4.26 ± 1.88	Controlvalue	3.35 ± 1.34
Values are quoted as mean + S.D. (n =6). ^TIndicates these values are significantly greater than control values (Student'st-test,P <0.05).

Antibiotic treatment

Treatment of individuals with neomycin sulphate, at a rate usually employed to sterilize or reduce the bacterial population within the colon prior to bowel surgery, had no statistically significant (t-test) effect on subsequent urinary methylamine excretion.

Applicant's summary and conclusion

Conclusions:

None of food products, containing representatives from the meat, fish & seafood, fruit & vegetable, dairy produce & cereal categories, produced large increases in urinary MMA output following ingestion. Slight increases following consumption of several fish & seafoods including clam, crab, haddock, halibut, octopus & tuna as well as the fruit and vegetables, pear, peas and tomato. Values after plaice, banana and bread consumption raised. The major source of human urinary methylamine is endogenous with contributions from the diet. Ingestion of creatinine also increased urinary methylamine levels.

Executive summary:

Mitchell et al. investigated in 2001 the excretion of MMA after ingestion of different dietary sources. Methylamine is the simplest aliphatic amine found in human urine. The average daily output of methylamine was 11.00 ± 8.17 mg (12.73 ± 9.35 male; 9.27 ± 6.35 female) with a range of values spreading from 1.68 to 62.30 mg. Dietary studies suggested that certain fish and seafoods (clam, crab, haddock, halibut, octopus, tuna) and fruit and vegetables (pear, peas, tomato) may add to this urinary output. Ingestion of creatinine also increased urinary methylamine levels.Chemical and dietary precursor studies indicated that there was no major exogenous source of this amine and suggested that the origin of the majority of human urinary methylamine is endogenous with only subtle contributions from the diet. Additionally pretreatment with neomycin sulfate showed that endogenous bacterial metabolism does not contribute to a significant production and urinary excretion of methylamine.