Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
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:
The effects of administrations of HCl, NH4CI and NH4HCO3 on the excretion of urea and ammonium in man
Author:
Fine A et al.
Year:
1977
Bibliographic source:
European Journal of Clinical investigation (1977) 7, 587-589

Materials and methods

Type of study / information:
Study on effects of oral HCl, NH4CI and NH4HCO3 on urinary nitrogen excretion in man.
Endpoint addressed:
basic toxicokinetics
Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (urine)

EXPOSURE LEVELS: 200 mmol divided into four aliquots were ingested daily on three separate study periods and there was a control period

EXPOSURE PERIOD: four 4 day periods, randomized, and at 2 week intervals

POSTEXPOSURE PERIOD: 24 h

DIET: Protein intake 1 g/24 h/kg, as milk, was constant throughout and 3 litres fluid ingested per day

MEASUREMENT:
Blood and urinary urea, urinary NH4, plasma glutamine

Results and discussion

Results:
In man, HCI acidosis reduces blood and urinary urea with a concomitant rise in ammonium (NH4+) excretion. Significantly less urea is excreted following NH4Cl administration than following equimolar ingestion of NH4HCO3. The results of these alterations in nitrogen excretion are interpreted in terms of bicarbonate utilization and production.

Any other information on results incl. tables

Alterations in urea and NH4+ production following the daily administration of 200 mmol HCl, NH4Cl and NH4HCO3, as compared to a control period in four normal subjects. Figures refer to mean ± S.E.M. of values obtained during the last day of each period. Individual values are given where relevant:

Control NH4HCO3
Day 1 Day 2 Day 3 Day 4 Day 1 Day 2 Day 3 Day 4
Plasma CO2 mmol/l) 26 ± 0.6 26 ± 0.8*
Plasma glutamine (mmol/l) 0.583 ± 0.037 0.528 ± 0.062
Blood urea (mmol/l) 5.93 ± 0.45 5.68 ± 0.4
Subject 1 7.13 6.84
2 6.06 5.92
3 5.55 5.22
4 5 4.84
Urine urea (mmol/24 h) 351 ± 9 477 ± 22#
Subject 1 382 361 373 366 418 432 422 427
2 361 340 320 347 427 457 462 472
3 305 299 314 326 427 447 445 477
4 346 327 348 364 546 517 522 530
Urine NH4+ (mmol/24 h) 33 ± 3 39 ± 4#
Subject 1 32 37 34 34 38 36 37 37
2 44 47 36 40 45 54 48 52
3 32 31 33 35 35 39 30 37
4 36 34 28 24 30 30 29 32
Urine N (NH4+ urea N) 734 ± 17 990 ± 43*
Subject 1 800 759 780 766 874 900 881 881
2 766 727 676 734 899 968 972 996
3 642 629 661 687 889 933 920 991
4 728 688 724 752 1122 1064 1073 1092

* Significantly different from controls (P < 0.025)

# Significantly different from NH4Cl (P < 0.005)

Applicant's summary and conclusion