3-phenyl-L-alanine

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: fed with phenylalanine-excess diet in this study. Dosing of females from day 1-21 of pregnancy.

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 effects of dietary excess of phenylalanine on maintenance of pregnancy
and reproductive performance, including fetal growth in rats was examined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3-phenyl-L-alanine

EC Number:

200-568-1

EC Name:

3-phenyl-L-alanine

Cas Number:

63-91-2

Molecular formula:

C9H11NO2

IUPAC Name:

phenylalanine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

from day 1 to day 14 or 21 of pregnancy

Doses / concentrations

Dose / conc.:

5 other: %

No. of animals per sex per dose:

8 rats in the 5% Phenylalanine group
7 rats in the ad libitum control group
5 rats in the pair-fed control

Control animals:

yes

Details on study design:

Two experiments were carried out:
Experiment 1: the effect of amino acid-excess diets on maintenance of pregnancy was examined. For this purpose pregnant animals receiving the experimental diets were killed on day 14 of pregnancy and the products of conception (uterus, amniotic fluid, placenta, and fetuses) were weighed, because nutritionally induced fetal resorption begins on about day 10 of pregnancy.
Experiment 2: the effects of excess of phenylalanine on the nitrogen balance of the dams, the free
amino acid concentrations in maternal plasma and fetal brain and fetal growth were examined.

Examinations

Maternal examinations:

BODY WEIGHT: Yes, daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, daily

Fetal examinations:

Fetuses weights,
Litter size

Reproductive indices
Weight of products of conception,
placenta weight,
fetuses weights,
fetal resorptions

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

During pregnancy, daily food intakes initially increased gradually, but near term they decreased app
reciably in all pregnant rats.

Maternal developmental toxicity

Number of abortions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

no effects observed

Changes in number of pregnant:

no effects observed

Details on maternal toxic effects:

Pregnancy was maintained in 100% of the rats on diets with an excess of phenylalanine.
The weights of conception products were similar to those of the corresponding pair-fed control.
The litter size was normal in all.

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Fetal body weight changes:

effects observed, treatment-related

Description (incidence and severity):

Given excess phenylalanine, the weights of fetuses were significantly lower than those of the
control.

Reduction in number of live offspring:

no effects observed

Description (incidence and severity):

The litter size was normal in all.

Other effects:

no effects observed

Description (incidence and severity):

No changes in maternal plasma or fetal brain amino acid concentrations were observed in rats given phenylalanine-excess diet.
Fetal brain on diets with excess of phenylalanine were lower than the controls. This finding indicates that prenatal brain growth is severely and specifically affected by excess of aromatic amino acids.

Applicant's summary and conclusion

Conclusions:

This study on effects of dietary excess of phenylalanine on maintenance of pregnancy and reproductive performance, including fetal growth in rats showed that pregnancy was maintained in 100% of the rats on diets with the excess of phenylalanine; the weights of conception products were similar to those of the corresponding pair-fed control; the weights of fetuses were significantly lower than those of the control; the litter size was normal in all; did not result in appreciable alterations in plasma or brain amino acid concentrations.

Executive summary:

The effects of diet with an excess of phenylalanine on the maintenance of pregnancy and fetal growth in rat were investigated in this study. Female Sprague Dawley rats weighing about 190 g were fed on 6 % casein diet (a low protein diet) containing 5% Phenylalanine from day 1 to 14 or 21 of pregnancy (also the day of autopsy). Pregnancy was maintained in 100 % of the rats on diets with an excess of phenylalanine. During pregnancy, daily food intakes initially increased gradually but near term they decreased appreciably in all pregnant rats. With regard to phenylalane in excess, the body weight gain during pregnancy for the groups receiving phenylalane were almost comparable to that of the pair-fed control. In all animals given excess amino acid phenylalnine the weights of conception products were similar to those of the corresponding pair-fed controls. However, in most groups given excess amino acid phenylalanine, the weight of foetuses was significantly lower than those of the respective pair-fed controls. The average weight of the foetuses of the groups receiving 5% excess phenylalanine was 3.24 ± 0.29 g compared to 4.11 ± 0.22 g for their pair-fed control. The litter size was almost normal in all rats on excess amino acid diets compared to the controls. The concentrations of phenylalanine in the maternal plasma were not increased appreciably by excess amounts of phenylalanine in the diet. Ingestion of diet containing excess phenylalanine did not result in appreciable alterations in plasma or brain amino acid concentrations.