Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Reference
Reference Type:
publication
Title:
Comparative Effect of Intravenously Administered Anitrogenous Compounds on Uric Acid Synthesis in Chicken Fed a 20% Protein Diet
Author:
Karasawa Y, Tasaki I, Yokota HO, Shibata F
Year:
1973
Bibliographic source:
J.Nutr. 103:1208-1211

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
Four to 5 cockerels were fed 35 g of an experimental diet per kg body weight once a day for 5 days. Six hrs after the last fed cardiac, portal and ureter were catheterized using heparin as anticoagulant. Nitrogenous compounds infused in the present experiment were L-glutamine, L-asparagine, monosodium L-glutamate, glycine, L-threonine, L-lysine hydrochloride, ammonium acetate and inosine. Each nitrogenous compound was dissolved in 5% glucose solution, and the test solution was adjusted to pH 7.4 with sodium hydroxide or hydrochloric acid solution. Six hrs after feeding the birds on day 5 the test solution was continuously infused into the portal vein through the portal catheter with a speed-controlled injector for 60 minutes. The infusion rate of test compounds except inosine was 0.1 mmole (glutamine, asparagine and lysine were 0.2 mEq of nitrogen and glutamic acid, glycine, threonine and ammonium acetate were 0.1 mEq) per kilogram of body weight per minute throughout the experiment, and that of inosine was 16.6 µmoles (66 /Eq of nitrogen). A control infusion was conducted with 5% glucose solution. About 2 ml of blood was collected through the cardiac catheter just before the infusion and 10, 20, 40 and 60 minutes after the first sampling. Total urine was collected through the right and left ureter catheters for 50 minutes during the infusion. Plasma and urinary uric acid were determined by the methods reported by Dubbs et al.and Pudelkiewicz et al., respectively.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed

Test animals

Species:
other: chicken
Strain:
other: single-comb white leghorn
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): 35 g of an experimental diet per kg bw once a day for 5 days, the diet was consumed within 40 min.
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: 5% glucose solution
Details on exposure:
Test solutions were administered at a rate of 0.1 mmole/kg bw/min for 60 min.
Doses:
0.1 mmole/kg bw/min (792 mg/kg bw/h)
No. of animals per sex per dose:
4 to 5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 60 min during infusion

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
other: increase of plasma uric acid concentration
Effect level:
5.6 other: mg/100 mL plasma
Based on:
act. ingr.
Key result
Sex:
male
Dose descriptor:
other: increase of urinary uric acid concentration
Effect level:
142.7 other: urinary uric acid excretion (mg/50 min)
Based on:
act. ingr.
Mortality:
not determined
Clinical signs:
not determined
Body weight:
not specified
Gross pathology:
not determined

Applicant's summary and conclusion

Conclusions:
In the present study the effect of infusion of several amino acids on uric acid synthesis in chicken was determined. In fusion of in total 792.7 mg/kg bw asparagine resulted in an increase of plasma uric acid of 5.6 mg/100 mL plasma and in an increase of urinary uric acid of 142.7 mg/ 50 min of infusion. Therefore, asparagine is considered to be readily metabolised via urea cycle.