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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyl 3-hydroxybutyrate
EC Number:
258-658-1
EC Name:
Butyl 3-hydroxybutyrate
Cas Number:
53605-94-0
Molecular formula:
C8H16O3
IUPAC Name:
butyl 3-hydroxybutanoate
Test material form:
other: colorless liquid
Details on test material:
The test substance, identified as n-butyl-3-hydroxybutyrate, Sample ID #: 30705-83-df, was received on June 6, 2013 and was further identified with PSL Reference Number 130606-50. The test substance was stored at room temperature, in the dark. The sample was administered as received. Documentation of the methods of synthesis, fabrication, or derivation of the test substance is retained by the Sponsor. The following information related to the characterization of the test substance was provided by the Sponsor:
Composition: n-butyl-3-hydroxybutyrate- I 00%, CAS #53605-94-0
Physical Description: Colorless liquid
pH:6
Solubility: The aqueous solubility is 3.9 weight%.
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: Stable for the duration of testing.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g. toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature and Relative Humidity Ranges: 19-220C and 57-70%, respectively.

Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.

Photoperiod: 12-hour light/dark cycle

Acclimation Period: 15-20 days

Food: Harlan Teklad Global 16% Protein Rodent Diet® #2016. The diet wasavailable ad libitum, except during fasting.

Water: Filtered tap water was supplied ad libitum.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

Cage: Each cage was identified with a cage card indicating at least the study number, dose level, identification, and sex of the animal.

Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number was attached to the rat. This number, together with a sequential animal number assigned to study number 36765, constituted unique identification.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Selection of Animals
Prior to each dosing, experimentally naive rats were fasted overnight by removing the feed from their cages. During the fasting period, the rats were examined for health and weighed (initial). Three healthy naive female rats (not previously tested) were selected for test.

Dose Calculations
Individual doses were calculated based on the initial body weights, taking into account the density (determined by PSL) of the test substance.

Dosing
The test substance was administered to the stomach using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3-4 hours after dosing.



Doses:
5000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Body Weights
Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing.

Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing ~nd at least once daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Necropsy
All rats were euthanized via C02 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
Statistical analysis was limited to the calculation of the mean.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 5 000 mg/kg bw
Mortality:
none
Clinical signs:
other: All animals survived test substance administration, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any
Gross pathology:
no abnormalities

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of this study, the acute oral LD50 of n-butyl-3-hydroxybutyrate is greater than 5,000 milligrams per kilogram of body weight in female rats.
Executive summary:

An acute oral toxicity test was conducted with rats to determine the potential for n-butyl-3-hydroxybutyrate to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 5,000 mg/kg of body weight in female rats. ' An initial limit dose of 5,000 mglkg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, two additional females received the same dose level, simultaneously. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice. All animals survived test substance administration, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.