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Toxicological information

Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Review on effectness of the test substance in patients, limited details.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998

Materials and methods

Type of study / information:
Alternative pathway therapy for urea cycle disorders
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In man the major pathway for the disposal of waste nitrogen is the urea cycle; in inborn errors of this pathway, nitrogen flux is reduced. As a result there is accumulation of ammonia and glutamine with disordered metabolism of other amino acids. Nitrogen homeostasis can be restored in these patients with a low-protein diet combined with compounds that create alternative pathways for nitrogen excretion.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
No data given

Results and discussion

Any other information on results incl. tables

The introduction of the test substance (typical 250 mg/kg bw/day, emergency 500 mg/kg bw/day) has been shown to be effective in the treatment of hyperammonaemia and disorders of the urea cycle. Limited side effects (mausea and vomiting) have been reported, but is acknowledged that side effects may be difficult to distinguish from hyperammonaemia since both may increase the uptake of tryptophan into the brain.

Applicant's summary and conclusion

Conclusions:
Nitrogen homeostasis can be restored with a low-protein diet combined with the test substance.
Executive summary:

In man the major pathway for the disposal of waste nitrogen is the urea cycle; in inborn errors of this pathway, nitrogen flux is reduced. As a result there is accumulation of ammonia and glutamine with disordered metabolism of other amino acids. Nitrogen homeostasis can be restored in these patients with a low-protein diet combined with compounds that create alternative pathways for nitrogen excretion.

The introduction of the test substance (typical 250 mg/kg bw/day, emergency 500 mg/kg bw/day) has been shown to be effective in the treatment of hyperammonaemia and disorders of the urea cycle. Limited side effects (mausea and vomiting) have been reported, but is acknowledged that side effects may be difficult to distinguish from hyperammonaemia since both may increase the uptake of tryptophan into the brain.