Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1975-1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only Summary, but Basic data given

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Sprague Dawley rats were dosed orally with valproic acid during 6 months.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Valproic acid
IUPAC Name:
Valproic acid
Details on test material:
- Name of test material (as cited in study report): Valproic acid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Remarks:
2%
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 months
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 79, 168, 341 mg/kg/day for males
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 97, 197,416 mg/kg/day for females
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
341 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Clinical examination, Bodyweight changes, Food and water intake, Hematology, Blood chemistry, Urinalysis, Myelograms, Organ weights, Macroscopic and microscopic examination
Dose descriptor:
NOAEL
Effect level:
416 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Clinical examination, Bodyweight changes, Food and water intake, Hematology, Blood chemistry, Urinalysis, Myelograms, Organ weights, Macroscopic and microscopic examination

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

After 6 months, all doses including the high dose were well tolerated and without toxic effect in the rat.

The only noteworthy findings were as follows :

- increased blood potassium after 3 months in male (341 mg/kg/day) and female (197 and 416 mg/kg/day),

- decrease in total protein and serum albumin in females (197 and 416 mg/kg) throughout the study, decrease in total protein in high-dose males and in albuminin males from all groups after 4.5 months,

- lymphocytosis after 3 months in mid-and high-dose females and after 4.5 months in mid-and high-dose males,

-  increase in thymus weight in all treated females and in relative kidney weight in all treated males with no apparent toxicological significance.

Applicant's summary and conclusion

Conclusions:
In a 6-month study, a NOAEL of 341 mg/kg/day was found for male Sprague-Dawley rats and a NOAEL of 416mg/kg/day for female Sprague-Dawley rats.