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Diss Factsheets

Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
data from in vivo study, which predates current guidance from the ECHA
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 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
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: 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 PSt Reference Number 130606-50. The test substance was stored at room temperature in a dry area protected from direct sunlight. The sample was applied 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- 100%, CAS #53605-94-0
Physical Description: Colorless liquid
pH:·6
Solubility: Not provided.
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: Stable. for the duration of testing.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Husbandry
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 58-76%, 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

4.A.5 Acclimation Period: 6 days

4.A.6 Food: Harlan Teklad Global High Fiber Rabbit Diet® #2031. A designated amount of the diet was available to each rabbit (approximately 150 grams/day).

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.

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

Animal: A number was allocated to each rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 36767, constituted unique identification.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy naive animals (not previously tested) without pre-existing skin irritation were selected for test. animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance.
Observation period:
Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours and at 7 days after patch removal. The· classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minutes, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals ( 4). The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period.
Number of animals:
3
Details on study design:
Primary Dermal Irritation Index Classification

0 Non-irritating
> 0-2.0 Slightly irritating
2.1 -5.0 Moderately irritating
> 5.0 Severely irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: overall
Score:
1.1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 168 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 168 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, n-butyl-3-hydroxybutyrate is considered to be slightly irritating to the skin.
Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for n-butyl-3-hydroxybutyrate to produce irritation after a single topical application. Under the conditions of this study, the test substance is considered to be slightly irritating to the skin. Five-tenths of a milliliter of the test substance was app1ied to the skin of three healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize et al. Within 24 hours after patch removal, all three treated sites exhibited very slight erythema and two treated sites exhibited very slight edema. The overall incidence and severity of irritation decreased gradually thereafter. Desquamation was noted for one animal by 24 hours. Although desquamation was noted for all three animal between 48 hours and Day 7, all animals were free of erythema and edema by Day 7 (study termination).

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