L-threonine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientific study not performed according to common guidelines. The feeding conditions in this study are very artificial which by itself might have significant influence on fetal growth.

Data source

Reference

Reference Type:

publication

Title:

The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats.

Author:

Matsueda S, Niiyama Y.

Year:

1982

Bibliographic source:

J Nutr Sci Vitaminol (Tokyo). 1982 Oct;28(5):557-73.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Scientific study in which the effect of amino acid-excess diets on maintenance of pregnancy as well as fetal growth was examined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

L-threonine

EC Number:

200-774-1

EC Name:

L-threonine

Cas Number:

72-19-5

Molecular formula:

C4H9NO3

IUPAC Name:

L-threonine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Doses / concentrations

Remarks:

Doses / Concentrations:
5 %
Basis:
nominal in diet

No. of animals per sex per dose:

6 rats in the 5% L-threonine group
7 rats in the ad libitum control group
5 rats in the pair-fed control

Control animals:

other: 6% casein diet ad libitum... (see attached file)

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Feeding of a 6% casein diet containing 5% added L-threonine to pregnant SD rats from day 1 to day 14 or 21 of pregnancy resulted in significant lower fetal weight than in ad libitum or pair-fed controls but no change in litter size. Excess L-threonine produced a significant reduction in brain weight, DNA, RNA, and protein that was not produced by food restriction. The maternal plasma concentration increased ca 13 -fold. Fetal brain concentration increased about 16 -fold.

Applicant's summary and conclusion

Executive summary:

Feeding of a 6% casein diet containing 5% added L-threonine to pregnant SD rats from day 1 to day 14 or 21 of pregnancy resulted in significant lower fetal weight than in ad libitum or pair-fed controls but no change in litter size. Excess L-threonine produced a significant reduction in brain weight, DNA, RNA, and protein that was not produced by food restriction. The maternal plasma concentration of L-threonine increased ca 13 -fold. Fetal brain concentration increased about 16 -fold.

However, the study was not performed according to common guidelines and the food conditions in this study are very artificial which by itself have significant influence on fetal growth. It is well known that restricted maternal protein supply perturbs fetal growth. Offspring of pregnant rats fed on protein-deficient diets are not only slightly smaller than controls fed on an adequate diet but also have permanent changes in the structure and function of their organs which result in reduced glucose tolerance and hypertension in adult life. Therefore, seen effects may be caused only by this extremely artificial situation of protein-restriction in combination with amino acid excess. Such situations are very artificial and unlikely for humans to occur.