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Diss Factsheets

Administrative data

Endpoint:
eye irritation, 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 405 (Acute Eye 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:
gas under pressure: refrigerated liquefied gas
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 instilled 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 1 iquid
pH: 6
Solubility: The aqueous solubility is 3.9 weight%.
Stability: Test substance was. expected to be stable for the duration oftesting.
Expiration Date: Stable for the duration of testing.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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 (Nat!. 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 Tempemture and Relative Humidity Ranges: 20-22°C and 66-78%, respectively.

Humidity was above the targeted upper limit for 2 days during the study. A portable dehumidifier was used to lower the humidity levels during this time.

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: 5 days

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.

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

Animal identification: A number was allocated to each mbbit 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 36766, constituted unique identification.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Prior to test initiation, both eyes of a group of animals were examined using a white light source and a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCI) after instillation of the fluorescein and then evaluated for corneal damage using an ultraviolet light source. Prior to test substance instillation, the eyes were re-examined and scored for abnormalities according to the "Scale for Scoring Ocular Lesions" (see Table 2). Three healthy animals (not previously tested) without pre-existing ocular irritation were selected for test.
Details on study design:
Prior to instillation, 2-3 drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic Solution USP, 0.5%) were placed into both the treated and control eye of each animal. One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The other eye of each rabbit remained untreated with the test substance and served as a control. The rabbits were then returned to their designated cages. The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period.

Ocular irritation was evaluated using a high-intensity white light in accordance with Draize et al. 1 (see Table 2) at 1, 24, 48, and 72 hours and at 4 and 7 days post· instillation. The fluorescein dye evaluation procedure described in Section S.A. was used in the treated eye at 24 hours and as needed at subsequent scoring intervals to evaluate the extent of corneal damage or to verify reversal of effects. Individual scores were recorded for each animi~,l. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted. The average score for all rabbits at each s~oring period was calculated to aid in data interpretation.

The time interval with the highest mean score (Maximum Mean Total Score- MMTS) for all rabbits was used to classify the test substance by the system ofKay and Calandra.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 1 hour
Score:
14
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 24 hrs
Score:
21
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 48 hrs
Score:
7
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 72 hrs
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 1 hr
Score:
14
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 24 hrs
Score:
21
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 48 hrs
Score:
19
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 72 hrs
Score:
14
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 96 hrs
Score:
7
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 168 hrs
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 1 hr
Score:
14
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 24 hrs
Score:
26
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 48 hrs
Score:
24
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 72 hrs
Score:
19
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 96 hrs
Score:
12
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 168 hrs
Score:
0
Max. score:
110
Reversibility:
fully reversible

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study. n-butyl-3-hydroxybutyrate is classified as moderately irritating to the eye.
Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for n-butyl-3- hydroxybutyrate to produce irritation from a single instillation via the ocular route. Under the conditions of this study, the test substance is classified as moderately irritating to the eye. / One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al. There was no iritis observed in any treated eye during this study. Within 24 hours of test substance instillation, all three treated eyes exhibited corneal opacity and 'positive' conjunctivitis. The overall incidence and severity of irritation decreased with time, and all animals were free of ocular irritation by Day 7 (study termination).