Phenylacetic acid

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Experimental maternal phenylketonuria: an examination of two animal models.

Author:

Loo YH, Rabe et.al.

Year:

1983

Bibliographic source:

Developmental Neuroscience 1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Toxicity of test chemical was assessed in Sprague -Dawley rats

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetic acid

EC Number:

203-148-6

EC Name:

Phenylacetic acid

Cas Number:

103-82-2

Molecular formula:

C8H8O2

IUPAC Name:

phenylacetic acid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 200-250 g

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

physiological saline

Details on exposure:

Sterile Saline (0.9% NaCl) solution of test chemical at pH 7.2-7.4, were infused at the rate of 20 ml

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

9th to 20th day of gestation

Frequency of treatment:

24hrs daily

Duration of test:

20 days

Doses / concentrations

Remarks:

7.5 -8.02umol/g/20ml and 6..5-7.0umol/g/20ml

Control animals:

yes, concurrent vehicle

Statistics:

Student’s test was used to determine the significance of differences between the control and each experimental group

Results and discussion

Effect levels

Dose descriptor:

LOAEL

Effect level:

0.2 other: umol/g

Based on:

test mat.

Sex:

female

Basis for effect level:

other: abortion, mortality rate increases, retarded growth of fetal body and brain, and a learning deficit among theprogeny.

Remarks on result:

other: effects observed

Observed effects

Learning deficits were observed in all litters tested. Body weight and cerebral hemisphere weight were significantly
l When plasma levels of unconjugated -test chemical were maintained above 0.5 umol/ml we observed spontaneous abortion and early deathof the newborn .

Applicant's summary and conclusion

Conclusions:

Subcutaneous infusion into pregnant rats from the 9th to 20th day of gestation of test chemical to elevate plasma levels of unconjugated test chemical to 0.25-0.60 uM/ml produced the syndrome of untreated maternal PKU: spontaneous abortion, mortality rate greater than normal among the newborn, retarded growth of fetal body and brain, and a learning deficit among the progeny.

Executive summary:

Subcutaneous infusion into pregnant rats from the 9^thto 20th day of gestation of test chemical to elevate plasma levels of unconjugated test chemical to 0.25-0.60 uM/ml produced the syndrome of untreated maternal PKU: spontaneous abortion, mortality rate greater than normal among the newborn, retarded growth of fetal body and brain, and a learning deficit among the progeny.